Salvage skull base surgery after proton beam therapy for recurrent sinonasal malignancies: A retrospective study.

BACKGROUND: This study aimed to examine treatment outcomes and postoperative complications associated with salvage skull base surgery following radical proton beam therapy (PBT). METHODS: Nine patients who underwent salvage skull base surgery following curative PBT as the initial treatment at our institution between September 2002 and May 2023 were retrospectively reviewed. RESULTS: The cohort comprised four males and five females with a mean age of 48.1 years. The average proton dose administered during initial therapy was 68.5 Gy (relative biological effectiveness). Among the salvage surgeries, eight were anterior skull base surgeries, and one was an anterior middle skull base surgery. No local recurrences or perioperative deaths were observed. Postoperative complications occurred in three patients (33.3%), all experiencing surgical site infections, with one also having cerebrospinal fluid leakage. CONCLUSION: The study demonstrates that salvage skull base surgery after PBT effectively achieves local control and safety in patients with recurrent sinonasal malignancies.

Risk factors for late postoperative bleeding after partial glossectomy for tongue cancer.

BACKGROUND: Partial glossectomy is the most common procedure for early-stage tongue cancer. Although late postoperative bleeding occasionally occurs, the associated risk factors have not been adequately identified. AIMS/OBJECTIVES: We aimed to investigate the rate and risk factors for late postoperative bleeding after transoral partial glossectomy with or without neck dissection for tongue cancer at our institution. MATERIAL AND METHODS: We analysed 211 patients who had undergone transoral partial glossectomy between January 2016 and January 2023. The potential risk factors associated with late postoperative bleeding were investigated using univariate and multivariate logistic regression analyses. RESULTS: Of the 211 patients, 40 (19%) showed late postoperative bleeding, with 19 (9%) classified as grade IIIa (Clavien-Dindo classification). Regarding all grades, late postoperative bleeding was significantly higher in patients aged <70 years and in those with polyglycolic acid (PGA) sheets (p = .046 and .030, respectively). For grade ≥ IIIa, late postoperative bleeding was significantly higher in patients with a history of anticoagulant/platelet administration, a mucosal defect covered with fibrin glue and a PGA sheet (p = .045 and .026, respectively). CONCLUSIONS AND SIGNIFICANCE: The findings of this study suggest that primary closure decreases the frequency of late postoperative bleeding.

Familial focal segmental glomerulosclerosis with Alport-like glomerular basement changes caused by paired box protein 2 gene variant.

Paired box protein 2 (PAX2) gene variant causes renal coloboma syndrome (MIM#120330). Further, they are associated with focal segmental glomerulosclerosis and characterized by basement membrane changes similar to Alport syndrome.Herein, we report an 8-year-old boy who presented with proteinuria and decreased renal function. His paternal uncle has focal segmental glomerulosclerosis and renal failure, and his paternal grandmother has renal failure and is receiving peritoneal dialysis. Further, his father has stage 2 chronic kidney disease. At 3 years of age, his serum creatinine-estimated glomerular filtration rate was 40-50 mL/min/1.73 m2. At 8 years of age, his renal function further decreased and he had proteinuria (urinary protein/Cr 3.39 g/g Cr). Renal histopathology showed oligonephronia and focal segmental glomerulosclerosis. A partial basket-weave pattern, similar to Alport syndrome, was also observed on a transmission electron microscope, and low-vacuum scanning electron microscopy revealed coarse meshwork changes in the glomerular basement membrane. Genetic analysis revealed a PAX2 heterozygous variant (NM_003987.4:c.959C  >  G), a nonsense variant in which the serine at position 320 changes to a stop codon, in our patient and his father. PAX2 is a transcription factor that is important for the podocyte variant. However, podocytes with PAX2 gene variants may cause abnormal basement membrane production and repair, thereby resulting in Alport-like changes.

Clinicopathological Features of Buccal Squamous Cell Carcinoma with Focus on Patients Who Never Smoke and Never Drink.

Introduction Oral carcinoma has been reported at a substantial proportion in patients who never smoke and never drink. However, the proportion may vary by subsite and ethnicity. Objective We aimed to determine the clinicopathological features of buccal squamous cell carcinoma (SCC) in a Japanese population. Methods We retrospectively analyzed the records of patients diagnosed with buccal SCC at our institution from September 2002 to November 2015. We reviewed the gender, age, tumor status, treatment, smoking, alcohol drinking, multiple primary cancers, and prognosis of the patients. The overall and cause-specific survival rates were calculated, and the effects of clinicopathological variables were assessed by univariate analysis. Furthermore, the cause of death was evaluated. Results Among the 63 patients (men: 38; women: 25) included in the present study, 29 (46.0%) never smoked or drank. Women were almost 5 years older than men ( p = 0.014). The number of women in the group who never smoked or drank was disproportionately higher than that of those in the smoker or drinker groups ( p < 0.001). In total, 29 patients (46.0%) had 59 multiple primary cancers, including 26 oral cancers. Surgeries and radiotherapy were performed in 57 (90.5%) and 6 (9.5%) cases, respectively. The 5-year overall survival and disease-specific survival rates were 74.6 and 78.8%, respectively. Conclusion Our study confirms that buccal SCC may develop in older adult Japanese patients, especially in women who have never smoked or drank. These patients could be at risk for second primary malignancy.

Characterization of Urate Metabolism and Complications of Patients with Renal Hypouricemia.

Objective Both renal hypouricemia (RHU) and gout are associated with renal dysfunction and urolithiasis. The difference in renal complications associated with RHU and gout, however, has not been studied. We characterized the urate metabolism and complications of patients with RHU and compared them with patients with gout. Methods Eighteen patients with RHU who had a serum uric acid (SUA) level <2 mg/dL (10 men and 8 women), 44 patients with gout (44 men) and 16 normouricemic patients (4 men and 12 women) were included. The blood and urinary biochemical data were evaluated. A genetic analysis of uric acid transporter 1 (URAT1) was also conducted in 15 cases with RHU. Results The SUA level of RHU was 0.9±0.5/mg/dL, and the Uur/Ucr and Cur/Ccr were 0.56±0.14% and 45.7±18.0%, respectively. A genetic analysis of URAT1 in 15 RHU patients showed that 13 harbored a URAT1 gene mutation, whereas 2 harbored the wild-type gene. The SUA level was significantly lower in RHU patients (n=11) than in either gout patients (n=44) or normouricemic patients (n=16). This reduction was accompanied by the elevation of Cua/Ccr. Urinary beta 2-microglobulin levels were higher in RHU patients than in gout or normouricemia patients. Cua/Ccr correlated with normalized urinary beta 2-microglobulin levels. The prevalence of urolithiasis was 18.2% in RHU cases and 6.8% in gout cases. A homozygous URAT1 mutation was associated with urolithiasis. Conclusion Besides urolithiasis, RHU can be associated with tubular dysfunction, such as elevated urinary beta 2-microglobulin levels.

Clinicopathological Features of Buccal Squamous Cell Carcinoma with Focus on Patients Who Never Smoke and Never Drink

Abstract Introduction Oral carcinoma has been reported at a substantial proportion in patients who never smoke and never drink. However, the proportion may vary by subsite and ethnicity. Objective We aimed to determine the clinicopathological features of buccal squamous cell carcinoma (SCC) in a Japanese population. Methods We retrospectively analyzed the records of patients diagnosed with buccal SCC at our institution from September 2002 to November 2015. We reviewed the gender, age, tumor status, treatment, smoking, alcohol drinking, multiple primary cancers, and prognosis of the patients. The overall and cause-specific survival rates were calculated, and the effects of clinicopathological variables were assessed by univariate analysis. Furthermore, the cause of death was evaluated. Results Among the 63 patients (men: 38; women: 25) included in the present study, 29 (46.0%) never smoked or drank. Women were almost 5 years older than men (p = 0.014). The number of women in the group who never smoked or drank was disproportionately higher than that of those in the smoker or drinker groups (p < 0.001). In total, 29 patients (46.0%) had 59 multiple primary cancers, including 26 oral cancers. Surgeries and radiotherapy were performed in 57 (90.5%) and 6 (9.5%) cases, respectively. The 5-year overall survival and disease-specific survival rates were 74.6 and 78.8%, respectively. Conclusion Our study confirms that buccal SCC may develop in older adult Japanese patients, especially in women who have never smoked or drank. These patients could be at risk for second primary malignancy.

Immunological and Genetic Characterization of Patients With Head and Neck Cancer who Developed Recurrence.

BACKGROUND/AIM: The recurrence rate of head and neck squamous cell carcinoma (HNSCC) remains high; thus the control of recurrence is a clinical problem to be challenged. To clarify the precise mechanism, specific immunological biomarkers responsible for recurrence were investigated. PATIENTS AND METHODS: The expression levels of immune response-associated and Shizuoka Cancer Center 820 cancer-associated genes, and genetic mutations from whole-exome sequencing were compared between HNSCC patients who developed recurrence (n=8) and HNSCC patients who did not develop recurrence (n=19) using a volcano plot analysis. Cytokine and epithelial-mesenchymal transition marker genes were analyzed using quantitative PCR. Tumor-infiltrating lymphocytes, immune checkpoint molecules, and human papilloma virus status were investigated using immunohistochemistry (IHC). RESULTS: Twenty-seven evaluable patients with HNSCCs received radiation therapy after surgery. Recurrence was identified in 8 patients. TP53 mutations tended to be higher in patients who developed recurrence than in those who did not develop recurrence (75% vs. 31.6%). Gene expression profiling showed the down-regulation of T cell activation genes (ICOS, CD69 and CD83) and the upregulation of the ERBB4, EGFR, VEGF, HIF1A, TGFB1, TWIST1, IL-8, and PAX7 genes, which suggested the activation of the TP53 mutation-TGF-ß1-PAX7 pathway and epithelial-mesenchymal transition. Additionally, IHC indicated a tendency toward a reduction in T cell accumulation and an increase in M2-type macrophage infiltration in tumors that recurred. CONCLUSION: A TP53 mutation-mediated immune-suppressive state in the tumor microenvironment and TGF-ß1-PAX7-mediated EMT might contribute to the promotion of recurrence in patients with HNSCC after postoperative radiotherapy.

Hsp70 promotes maturation of uromodulin mutants that cause familial juvenile hyperuricemic nephropathy and suppresses cellular damage.

BACKGROUND: Familial juvenile hyperuricemic nephropathy (FJHN) is an autosomal dominant disorder caused by mutations in UMOD. Here we studied effects of genetic expression and pharmacological induction of Hsp70 on the UMOD mutants C112Y and C217G. METHODS: We expressed wild type (WT), C112Y and C217G in HEK293 cells and studied their maturation and cellular damage using western blot and flow cytometry. RESULTS: Expression of C112Y or C217G increased pro-apoptotic proteins, decreased anti-apoptotic proteins, and induced cellular apoptosis as examined by annexin V staining and flow cytometry. Overexpression of Hsp70 or administration of an Hsp70 inducer geranylgeranylacetone (GGA) promoted maturation of the mutant proteins, increased their secreted forms, normalized the levels of pro- and anti-apoptotic proteins and suppressed apoptosis. CONCLUSION: These findings indicated that Hsp70 enhanced maturation of C112Y and C217G and reduced cellular apoptosis, suggesting that Hsp70 induction might be of a therapeutic value for treatment of FJHN.

Predictive Model for Adverse Events and Immune Response Based on the Production of Antibodies After the Second-Dose of the BNT162b2 mRNA Vaccine.

BACKGROUND: The BNT162b mRNA vaccine for coronavirus disease 2019, which is caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), mimics the immune response to natural infection. Few studies have predicted the adverse effects (AEs) after the second-dose vaccination. We present a predictive model for AEs and immune response after the second-dose of the BNT162b mRNA vaccine. METHODS: To predict AEs, 282 healthcare workers (HCWs) were enrolled in this prospective observational study. The classification and regression tree (CART) model was established, and its predictive efficacy was assessed. To predict immune response, 282 HCWs were included in the analysis. Moreover, the factors affected by anti-SARS-CoV-2 spike protein RBD antibody (s-IgG) were evaluated using serum samples collected 2 months after the second-dose vaccination. The s-IgG level was assessed using Lumipulse G1200. Multiple regression analyses were conducted to evaluate variables associated with anti-s-IgG titer levels. RESULTS: The most common AEs after the second-dose vaccination were pain (87.6%), redness (17.0%) at the injection site, fatigue (68.8%), headache (53.5%), and fever (37.5%). Based on the CART model, headache after the first-dose vaccination and age < 30 years were identified as the first and second discriminators for predicting the headache after the second-dose vaccination, respectively. In the multiple linear regression model, anti-s-IgG titer levels were associated with age, female sex, and AEs including headache and induration at the injection site after the second-dose vaccination. CONCLUSION: Headache after the first-dose vaccination can be a predictor of headache after the second-dose vaccination, and AEs are indicators of immune response.

Physical Characteristics of Injection Site Pain After COVID-19 mRNA BNT162b2 Vaccination.

BACKGROUND: BNT162b2, an mRNA COVID-19 vaccine, was launched in many countries as an intramuscular vaccination for COVID-19 infection. Few studies have assessed the physical indications of pain at the immunization site. This study aimed to characterize pain at the injection site and investigate morphological attributes using ultrasound. METHODS: Forty-three of 211 healthcare workers who received a second dose of BNT162b2 between February 2021 and March 2021 were enrolled in the study. The mean age of the subjects was 40 years. We evaluated patients' pain at the injection site using the Numerical Rating Pain Scale (NRPS). We also assessed the thickness of the deltoid muscle fascia at the injection site by ultrasound. Bayesian robust correlation was employed to explore the relationship between the pain intensity scores and ultrasound measurements. RESULTS: All eligible subjects complained of pain at the injection site. A median pain onset of 8 hours post-vaccination and a median peak intensity score of 4 were reported. Onset of relief occurred after 2 days. Ultrasound images demonstrated a 2.5-fold increase in fascia thickness at the injection site without intramuscular echogenicity change in all subjects. A correlation was established between the NRPS score and the non-injection-to-injection-side ratio of fascia thickness at the injection site (rho = 0.66). CONCLUSION: A sore arm was the most prevalent side effect of BNT162b2 vaccination and could be attributed to temporal fasciitis.

Triplet induction chemotherapy followed by less invasive surgery without reconstruction for human papillomavirus-associated oropharyngeal cancers: Why is it successful or unsuccessful?

BACKGROUND: De-escalating treatments have been focused on for HPV-associated oropharyngeal squamous cell carcinoma (OPSCC). We assessed the efficacy of a triplet induction chemotherapy (ICT) followed by surgery with or without neck dissection (ND) for locally advanced OPSCC, aiming at less invasive surgery without free-flap reconstruction and avoiding postoperative irradiation. METHODS: This was a retrospective study of 41 patients with advanced resectable HPV-positive OPSCC who underwent ICT followed by surgery of primary resection with or without ND. Patients underwent triplet ICT, including docetaxel, cisplatin, and 5-fluorouracil, or carboplatin, paclitaxel, and cetuximab. RESULTS: Twenty-nine patients had tonsillar cancer, 15 patients were current smokers, and 18 and 12 patients had T2N1M0 and T1N1M0 status (UICC 8th), respectively. After ICT, a surgical procedure without free-flap reconstruction and tracheostomy was possible in 90.2%. Pathological complete response at both the primary site and lymph nodes was achieved in 73.2%. Of the patients who underwent surgery, no adjuvant radiotherapy was required in 85.0%. Two patients (4.9%) experienced recurrence at regional lymph nodes, but were cured by salvage ND followed by adjuvant radiotherapy. CONCLUSIONS: Upfront ICT using highly responsive triplet chemotherapeutic regimens may enable us to perform less invasive surgery without free-flap reconstruction and to avoid postoperative irradiation to the locoregional field through excellent postoperative pathological features.

Effects of depression on the condition of older inpatients with fracture and preexisting cognitive impairment.

AIM: Few studies of depression have examined older inpatients with fracture and preexisting cognitive impairment. The current study sought to confirm whether depression affects the condition of older inpatients with fracture who also have cognitive impairment, and to investigate the extent to which depression affects activities of daily living. METHODS: This was a retrospective cross-sectional study. The subjects were older inpatients with fracture and preexisting cognitive impairment. We examined data within 1 week of hospitalization, obtained from medical records. The data included demographic information, the motor Functional Independence Measure, Charlson Comorbidity Index, Mini-Mental State Examination, Geriatric Depression Scale 15, Geriatric Nutritional Risk Index, Skeletal Muscle Index and maximum grip strength test. These variables were compared between the two groups (with and without depression), and multiple regression analysis was performed with the motor Functional Independence Measure as the dependent variable. RESULTS: The subjects were 68 patients. Only the motor Functional Independence Measure was significantly lower in the depression group than the non-depression group. Multiple regression analysis confirmed that depression strongly affected activities of daily living. CONCLUSIONS: In considering the recovery of older inpatients with fracture and preexisting cognitive impairment, it is important to take the effects of depression into account.Implications for rehabilitationThe number of older fracture inpatients with cognitive impairment is predicted to increase, and such patients have a high prevalence of depression.Depression strongly affected Activities of Daily Living in older inpatients with fracture and pre-existing cognitive impairment.Focusing on depression assessment and intervention is important for rehabilitation of older fracture inpatients with cognitive impairment.

Successful Treatment of Cyst Infection in an Infant With Autosomal Dominant Polycystic Kidney Disease Using Trimethoprim/Sulfamethoxazole.

Autosomal dominant polycystic kidney disease (ADPKD) is the most common genetic disease causing renal cysts. Reports on kidney cyst infection in children are rare despite cyst infections being important complications of ADPKD. Here, we report a case of a child without any medical history who had a urinary tract infection with sepsis at 7 months. Leukocyturia persisted despite antibiotic therapy because the infection was treatment-resistant. Initial ultrasound and contrast computed tomography were inconclusive because cysts could not be detected clearly, and a family history of renal cysts was not determined. Subsequently, history of paternal renal cysts, thick walls in infectious cystic lesions on diffusion-weighted magnetic resonance imaging (MRI), and multiple small lesions with high signals on T2-weighted imaging in both kidneys became apparent. Upon diagnosis of ADPKD with cyst infection, antibiotic therapy was switched from cefotaxime to trimethoprim/sulfamethoxazole to achieve better cyst penetration, which successfully resolved the infection. In this patient, MRI was effective for clear visualization and diagnosis of infectious lesions and small cysts in undiagnosed ADPKD with cyst infection. Administering antibiotics with better cyst penetration is important. Trimethoprim/sulfamethoxazole is an option for use in children. This is the first case report that describes ADPKD with cyst infection in an infant in detail.

Low-vacuum scanning electron microscopy may allow early diagnosis of human renal transplant antibody-mediated rejection.

Antibody-mediated rejection (ABMR) is an important cause of both short- and long-term injury to renal allografts. Transplant glomerulopathy (TG) is strongly associated with ABMR and reduced graft survival. Ultrastructural changes in early-stage ABMR include TG as a duplication of the glomerular basement membrane (GBM), which can be observed only by transmission electron microscopy (TEM). Low-vacuum scanning electron microscopy (LVSEM) is a new technique that allows comparatively inexpensive, rapid, and convenient observations with high magnification. We analyzed human renal transplants using LVSEM and evaluated the ultrastructural changes representing TG in ABMR. GBM duplication was more clearly visible in the LVSEM images than in the light microscopy (LM) images. In the ABMR group, the cg score of the Banff classification was higher in 54% (7/13) of specimens for LVSEM images than for LM images. And 4 specimens exhibited duplication of the GBM analyzed by LVSEM, but not by LM. In addition, three-dimensional ultrastructural changes, such as coarse meshwork structures of GBM, were observed in ABMR specimens. The ABMR group also exhibited ultrastructural changes in the peritubular capillary basement membranes. In conclusion, analyses of renal transplant tissues using LVSEM allows the identification of GBM duplication and ultrastructural changes of basement membranes at the electron microscopic level, and is useful for early-stage diagnosis of ABMR.

A review of clinical characteristics and genetic backgrounds in Alport syndrome.

Alport syndrome (AS) is a progressive hereditary renal disease that is characterized by sensorineural hearing loss and ocular abnormalities. It is divided into three modes of inheritance, namely, X-linked Alport syndrome (XLAS), autosomal recessive AS (ARAS), and autosomal dominant AS (ADAS). XLAS is caused by pathogenic variants in COL4A5, while ADAS and ARAS are caused by those in COL4A3/COL4A4. Diagnosis is conventionally made pathologically, but recent advances in comprehensive genetic analysis have enabled genetic testing to be performed for the diagnosis of AS as first-line diagnosis. Because of these advances, substantial information about the genetics of AS has been obtained and the genetic background of this disease has been revealed, including genotype-phenotype correlations and mechanisms of onset in some male XLAS cases that lead to milder phenotypes of late-onset end-stage renal disease (ESRD). There is currently no radical therapy for AS and treatment is only performed to delay progression to ESRD using nephron-protective drugs. Angiotensin-converting enzyme inhibitors can remarkably delay the development of ESRD. Recently, some new drugs for this disease have entered clinical trials or been developed in laboratories. In this article, we review the diagnostic strategy, genotype-phenotype correlation, mechanisms of onset of milder phenotypes, and treatment of AS, among others.

Relevant factors of depression in dementia modifiable by non-pharmacotherapy: a systematic review.

Depression in dementia patients is associated with complications such as decreased activities of daily living and decreased quality of life. Because pharmacotherapeutic treatments for depression in dementia patients may have a poor risk-benefit ratio, effective non-pharmacotherapeutic interventions are favourable. However, the development of effective treatments requires the identification of depression-associated factors that can be modified by non-pharmacotherapeutic means in dementia patients. This systematic literature review aimed to identify modifiable factors related to depression and confirm that these factors can be improved by non-pharmacotherapeutic interventions. We searched PubMed, SpringerLink, the Web of Science, and the Cochrane Library for articles published between June 2007 and June 2017. We included studies that investigated causes of depression in dementia patients and excluded studies with unclear dementia diagnostic criteria or operational definitions. Of 9004 records screened, 6 studies were included. The participants included community-dwelling individuals and long-term care facility residents. The severity of dementia varied from mild to severe. After reviewing the studies, we identified five modifiable relevant factors in community-dwelling individuals: (i) pain; (ii) neuropsychiatric symptoms; (iii) cognitive decline; (iv) social isolation; and (v) quality of life. In long-term care facility residents, we identified neuropsychiatric symptoms and quality of life as relevant factors. Our results indicated that non-pharmacological interventions that improve these factors may improve symptoms of depression. A longitudinal study is recommended to clarify the mechanisms underlying depression symptoms and treatment in dementia patients. In addition, further investigation is needed to elucidate the ways in which differing dementia types and severity affect symptoms of depression.

Qualitative Analysis of the Psychosocial Adaptation Process in Children with Chronic Kidney Disease: Toward Effective Support During Transition from Childhood to Adulthood.

BACKGROUND: Pediatric chronic renal disease only shows abnormal values in a urinalysis in the initial stage, and subjective signs and symptoms are rare. If adolescents with chronic renal disease face a disease crisis combined with the usual developmental crisis, this may cause psychosocial maladaptation. We analyzed psychosocial adaptation in Japanese children with chronic renal disease in order to identify factors influencing healthy adaptation. METHODS: Ten children and adult patients with chronic kidney disease attending Tottori University Hospital, Japan in 2016 participated in a semi-structured interview (a modified version of the grounded theory approach) comprising questions about episodes since disease onset and thoughts/feelings at onset. RESULTS: Twenty-four concepts extracted from the data were sorted into 5 categories. These concepts and categories were expanded on an orthogonal axis with time and self-esteem in order to establish an adaptation model for children with chronic kidney disease. Category names are as follows. (Cat. 1: Emotional impact on being informed of disease, Cat. 2: Social challenges of treatment and resulting identity diffusion, Cat. 3: Emotional conflict on school return, Cat. 4: Resilience and related factors, Cat. 5: Re-establishment of identity). CONCLUSION: Since pediatric chronic renal disease has few manifestations, it is difficult for patients to accept. Children facing a chronic disease crisis plus adolescent developmental crisis may show identity diffusion. In order for children to re-establish their identity and adapt to society, factors supporting resilience are important. Key factors include school life, interactions with friends, counseling by adult mentors and family acceptance. Healthcare professionals need to provide age-appropriate information on renal disease and support patients.

Morphological diagnosis of Alport syndrome and thin basement membrane nephropathy by low vacuum scanning electron microscopy.

Alport syndrome (AS) and thin basement membrane nephropathy (TBMN) are genetic disorders caused by mutations of the type IV collagen genes COL4A3, COL4A4, and/or COL4A5. We here aimed to investigate the three-dimensional ultrastructure of the glomerular basement membrane (GBM) in order to introduce a novel method of diagnosing AS and TBMN. The subjects were 4 patients with AS and 6 patients with TBMN. Conventional renal biopsy paraffin sections from AS and TBMN patients were stained with periodic acid methenamine silver (PAM) and observed directly under low vacuum scanning electron microscopy (LVSEM). The PAM-positive GBMs were clearly visible under LVSEM through the overlying cellular components. The GBMs showed characteristic coarse meshwork appearances in AS, and thin and sheet-like appearances in TBMN. At the cut side view of the capillary wall, the GBMs in AS appeared as fibrous inclusions between a podocyte and an endothelial cell, while the GBMs in TBMN showed thin linear appearances. These different findings of GBMs between AS and TBMN were easily observed under LVSEM. Thus, we conclude that three-dimensional morphological evaluation by LVSEM using conventional renal biopsy paraffin sections will likely be useful for the diagnosis of AS and TBMN, including for retrospective investigations.

Clinical overview of nephrogenic diabetes insipidus based on a nationwide survey in Japan.

BACKGROUND: Nephrogenic diabetes insipidus (NDI) is a rare disease whose complications include polyuria, renal dysfunction, growth disorder and mental retardation. The details of NDI's clinical course have been unclear. To address this uncertainty, we performed a large investigation of the clinical course of NDI in Japan. METHODS: Between December 2009 and March 2011, we provided a primary questionnaire to 26,282 members of the Japan Endocrine Society, the Japanese Urological Association, the Japanese Society for Pediatric Endocrinology, the Japanese Society for Pediatric Nephrology, the Japanese Society of Nephrology, the Japanese Society of Neurology and the Japanese Society of Pediatric Urology. In addition, we provided a secondary questionnaire to 121 members who reported experience with cases of NDI. We asked about patient's age at onset, diagnosis, complications, effect of treatment and patient's genotype. RESULTS: We enrolled 173 patients with NDI in our study. Of these NDI patients, 143 were congenital and 30 were acquired. Of the 173, 73 patients (42%) experienced urologic complications. Among the 143 with congenital NDI, 20 patients (14%) had mental retardation. Patients with NDI mainly received thiazide diuretics, and some patients responded to treatment with desmopressin acetate (DDAVP). Gene analyses were performed in 87 patients (61%) with congenital NDI, revealing that 65 patients had an arginine vasopressin receptor type 2 (AVPR2) gene mutation and that 8 patients (9.2%) had an aquaporin 2 (AQP2) gene mutation. Patients with the AVPR2 mutation (D85N) generally showed a mild phenotype, and we found that DDAVP was generally an effective treatment for NDI among these patients. CONCLUSION: We suggest that adequate diagnosis and treatment are the most important factors for improving prognoses. We further suggest that gene analysis should be performed for optimal treatment selection and the early detection of NDI among siblings.

A novel approach to the histological diagnosis of pediatric nephrotic syndrome by low vacuum scanning electron microscopy.

Despite intensive treatment, steroid-resistant nephrotic syndrome (NS) often progresses to endstage renal disease. Therefore, a more accurate and quick histological diagnosis is required to properly treat such patients. The aim of this study was to introduce a novel approach to the histological diagnosis of pediatric NS by low vacuum scanning electron microscopy (LVSEM) and to describe the morphological differences in glomeruli between steroid-sensitive and steroid-resistant NS specimens. The subjects were three patients with steroid-sensitive NS and four patients with steroid-resistant NS. Conventional renal biopsy paraffin sections were stained with platinum-blue (Pt-blue) or periodic acid methenamine silver (PAM) and directly observed under LVSEM at magnifications between ×50 and ×10,000. The Pt-blue-stained sections showed three-dimensional structural alterations in glomerular podocytes and foot processes. PAM-stained sections showed changes in the structure and thickness of the glomerular basement membrane (GBM). Consequently, many round-shaped podocytes and elongated primary foot processes were exclusively recognized in steroid-resistant NS, although irregularities in foot process interdigitation, fusions, effacements, and microvillus transformations were observed in both steroid-sensitive and steroidresistant NS. Irregularities in thickness and the wrinkling of GBMs were clearly detected in steroid-resistant NS. The evaluation by LVSEM is probably useful for the renal histological diagnosis of pediatric NS.