CFAP47 is a novel causative gene implicated in X-linked polycystic kidney disease.

Autosomal dominant polycystic kidney disease (ADPKD) is a well-described condition in which ~80% of cases have a genetic explanation, while the genetic basis of sporadic cystic kidney disease in adults remains unclear in ~30% of cases. This study aimed to identify novel genes associated with polycystic kidney disease (PKD) in patients with sporadic cystic kidney disease in which a clear genetic change was not identified in established genes. A next-generation sequencing panel analyzed known genes related to renal cysts in 118 sporadic cases, followed by whole-genome sequencing on 47 unrelated individuals without identified candidate variants. Three male patients were found to have rare missense variants in the X-linked gene Cilia And Flagella Associated Protein 47 (CFAP47). CFAP47 was expressed in primary cilia of human renal tubules, and knockout mice exhibited vacuolation of tubular cells and tubular dilation, providing evidence that CFAP47 is a causative gene involved in cyst formation. This discovery of CFAP47 as a newly identified gene associated with PKD, displaying X-linked inheritance, emphasizes the need for further cases to understand the role of CFAP47 in PKD.

[Pathological Complete Response and Long-Term Survival of a Gastric Neuroendocrine Carcinoma Patient Treated by Neoadjuvant Chemotherapy].

A 64-year-old man with gastric tumor in the antrum had been diagnosed with gastric neuroendocrine carcinoma(NEC) by biopsy and multiple lymph node metastases(#3 and #6)by abdominal computed tomography. After staging laparoscopy showed that there were no non-curative factors, neoadjuvant chemotherapy(S-1/cisplatin[CDDP]: 2 courses)and distal gastrectomy and D2 lymph node dissection were performed. The pathological diagnosis was shown as pathological complete response(pCR). After adjuvant chemotherapy(S-1/CDDP: 2 courses, S-1: 6 courses)was administered, the patient is alive at 8 years without recurrence.

[A Case of Long-Term Survival by Multidisciplinary Surgical Treatment for Metastatic Multi-Organ Metastasis after Radical Resection of Esophageal Cancer].

A 78-year-old man with advanced thoracic esophageal cancer underwent radical esophagectomy after neoadjuvant chemotherapy with cisplatin plus 5-FU. He had left adrenal metastasis 10 months after surgery and removed it, but 3 months later he had liver metastases. After 2 courses of chemotherapy with nedaplatin plus 5-FU, resection was performed. One course of nedaplatin plus 5-FU for adjuvant chemotherapy was added, but the patient was followed up without another chemotherapy after surgery because of intestinal obstruction due to infection and increase of the lymphatic cyst in the abdominal cavity. Six months after the liver resection, nodules appeared in the right lung, and 4 months later, multiple nodules extending to both lungs were observed. Therefore, it was judged that there were multiple lung metastases, and administration of nivolumab was started. He has been 3 years since the recurrence of esophageal cancer and 17 months after the start of nivolumab administration, but the recurrence lesion is only progressing to lung metastasis.

Development of a risk stratification scoring system for deep vein thrombosis upon psychiatric admission.

AIM: Psychiatric patients have increased risk of deep vein thrombosis (DVT). However, there is no systematic data on risk assessment of DVT among psychiatric inpatients. The aim of this study was to develop a risk stratification scoring system for DVT among psychiatic patients on admission. METHODS: A systematic review of psychiatric patient's charts, who were admitted to the Tokyo Metropolitan Matsuzawa Hospital from June 2012 to February 2016 and underwent screening for DVT, was conducted. Patients were randomly divided into development (n = 2634) and validation (n = 2634) groups. Estimated risk values in the multiple logistic regression model for the development sample were rounded to the nearest integer, and used as points of associated factors in the risk stratification scoring system; the total scores were tested in the validation sample. The score's discriminatory ability was assessed with the area under the receiver operating characteristic curve (AUC). RESULTS: Among the 5268 patients, 258 (4.9%) had DVT. Advancing age, female sex, active cancer, previous venous thromboembolism, transfer from a general hospital, catatonia, and major depressive episode were all significantly associated with the presence of DVT in the development sample. The total score showed good discriminatory ability in the validation sample (AUC: 0.816, 95% confidence interval: 0.781-0.851); scores of 0-1, 2-3, 4-5, and ≥ 6 were associated with very low risk (0.7%), low risk (4.6%), moderate risk (14.9%), and high risk (35%) for DVT, respectively. CONCLUSION: Our risk stratification scoring system showed good performance for detection of DVT among psychiatric patients on admission.

[A Case of Long-Term Survival Achieved after Nivolumab Treatment for Recurrence of Postoperative Advanced Gastric Cancer].

A 75-year-old man with a Type 3 advanced gastric cancer in the middle gastric body and paraaortic lymph node swelling was treated chemotherapy. After treatment, we performed an exploratory laparotomy and curative total gastrectomy. As adjuvant chemotherapy, S-1 treatment was administrated for 4 courses but multiple metastases from left supraclavicular to paraaortic lymph nodes. First, Cape plus CDDP plus T-mab therapy treated. Because of acute renal failure, Cape plus L-OHP plus T-mab was administrated but response evaluation was PD. In the second-line therapy, Ramucirumab plus paclitaxel was performed 4 courses. Third, we administrated Nivolumab. After 6 courses, response evaluation was PR and we continued 24 courses. At the same time, there was acute-onset Nivolumab-induced organizing pneumonia and we treated steroid pulse, azithromycin and introduced home oxygen therapy. At the present, 47 months long-term survival achieved after Nivolumab treatment.

Undifferentiated carcinoma of the transverse colon with rhabdoid features that developed during treatment of non-small cell lung carcinoma with pembrolizumab: a case report.

BACKGROUND: Undifferentiated carcinoma of the colon is rare, and its prognosis is very poor. We report a case of undifferentiated carcinoma of the colon with rhabdoid features developed during treatment of non-small lung carcinoma (NSCLC) with pembrolizumab. CASE PRESENTATION: A 58-year-old man was diagnosed with transverse colon cancer during chemotherapy with pembrolizumab for NSCLC. Laparoscopic right hemicolectomy was performed. The histopathological diagnosis was undifferentiated carcinoma with rhabdoid features and lymph node metastasis. Immunohistochemically, programmed death ligand 1 (PD-L1) showed positivity. The microsatellite instability (MSI) status was low. He continued to receive pembrolizumab for NSCLC, and there have been no signs of colon cancer recurrence and progression of NSCLC for 15 months. CONCLUSION: We present the case of an undifferentiated carcinoma of the transverse colon with rhabdoid features. The development of the tumor with the expression of PD-L1 during pembrolizumab might have been associated with the low MSI.

A three-dimensional computed tomography angiography study of the anatomy of the accessory middle colic artery and implications for colorectal cancer surgery.

PURPOSE: In the present study, we focused on the accessory middle colic artery and aimed to increase the safety and curative value of colorectal cancer surgery by investigating the artery course and branching patterns. METHODS: We included 143 cases (mean age, 70.4 ± 11.2 years; 86 males) that had undergone surgery for neoplastic large intestinal lesions at the First Department of Surgery at Yamagata University Hospital between August 2015 and July 2018. We constructed three-dimensional (3D) computed tomography (CT) angiograms and fused them with reconstructions of the large intestines. We investigated the prevalence of the accessory middle colic artery, the variability of its origin, and the prevalence and anatomy of the arteries accompanying the inferior mesenteric vein at the same level as the origin of the inferior mesenteric artery. RESULTS: Accessory middle colic artery was observed in 48.9% (70/143) cases. This arose from the superior mesenteric artery in 47, from the inferior mesenteric artery in 21, and from the celiac artery in two cases. In 78.2% (112/143) cases, an artery accompanying the inferior mesenteric vein was present at the same level as the origin of the inferior mesenteric artery; this artery was the left colic artery in 92, the accessory middle colic artery in 11, and it divided and became the left colic artery and the accessory middle colic artery in 10 cases. CONCLUSION: 3D CT angiograms are useful for preoperative evaluation. Accessory middle colic arteries exist and were observed in 14.9% of cases.

Self-rated cognitive functions following chemotherapy in patients with breast cancer: a 6-month prospective study.

PURPOSE: The purpose of the study was to evaluate subjective (self-rated), family-rated, and objective (researcher-rated) cognitive functions in patients with breast cancer after chemotherapy. METHOD: We conducted a prospective study to trace self-rated cognitive functions in 30 patients with breast cancer at the completion of chemotherapy (T0) and 6 months later (T1). Subjective cognitive functions were assessed with Cognitive Failures Questionnaire (CFQ), Dysexecutive Questionnaire (DEX-S), and Everyday Memory Checklist (EMC-S) for attention, executive function, and episodic memory, respectively. Their family members also completed DEX-I and EMC-I for executive function and episodic memory, respectively. We also examined objective cognitive functions. Self-rated cognitive functions were compared with the normative data. They were compared between T0 and T1. We calculated correlation coefficients between self-rated and other cognitive functions. RESULTS: At T0, 6 (20.0%) and 2 (6.7%) participants showed higher DEX-S and EMC-S scores than the normative data, respectively, while no participant had abnormal CFQ scores. At T1, DEX-S and EMC-S scores were normalized in 3 (50.0%) and 2 (100.0%) participants, respectively. No participant showed increases in CFQ scores. No changes were found in objective cognitive functions from T0 to T1. DEX-S and DEX-I or EMC-S and EMC-I scores were correlated at both T0 and T1, which did not survive multiple corrections. There was no association between subjective and objective cognitive functions. CONCLUSION: Impairments in subjective cognition may be transient after chemotherapy in patients with breast cancer. Furthermore, patients and their families appear to share similar prospects on their cognitive functions.

Isolation, Amino Acid Sequences, and Plausible Functions of the Galacturonic Acid-Binding Egg Lectin of the Sea Hare Aplysia kurodai.

Egg lectins occur in a variety of animals ranging from mollusks to vertebrates. A few examples of molluscan egg lectins have been reported, including that of the sea hare Aplysia kurodai; however, their biological functions in the egg remain unclarified. We report the isolation, determination of primary structure, and possible functions of A.kurodai lectin (AKL) from the egg mass of A. kurodai. We obtained AKL as an inseparable mixture of isoproteins with a relative molecular mass of approximately 32 kDa by affinity purification. The hemagglutinating activity of AKL against rabbit erythrocytes was inhibited most potently by galacturonic acid and moderately by xylose. Nucleotide sequencing of corresponding cDNA obtained by rapid amplification of cDNA ends (RACE) allowed us to deduce complete amino acid sequences. The mature polypeptides consisted of 218- or 219-amino acids with three repeated domains. The amino acid sequence had similarities to hypothetical proteins of Aplysia spp., or domain DUF3011 of uncharacterized bacterial proteins. AKL is the first member of the DUF3011 family whose function, carbohydrate recognition, was revealed. Treatment of the egg with galacturonic acid, an AKL sugar inhibitor, resulted in deformation of the veliger larvae, suggesting that AKL is involved in organogenesis in the developmental stage of A. kurodai.

Immediate vs Gradual Discontinuation in Antipsychotic Switching: A Systematic Review and Meta-analysis.

Background: Antipsychotic switching is routine in clinical practice, although it remains unclear which is the preferable switching method: immediate discontinuation of the current antipsychotic or a gradual tapering approach. The first strategy has been implicated in rebound/withdrawal symptoms and emergence/exacerbation of symptoms, whereas the gradual approach is thought to pose a risk of additive or synergistic side effects if employed in the context of a crossover approach. Methods: MEDLINE, Embase, and Cochrane Central Register of Controlled Trials were systematically searched. Randomized controlled trials examining immediate vs gradual antipsychotic discontinuation in antipsychotic switching in patients with schizophrenia and/or schizoaffective disorder were selected. Data on clinical outcomes, including study discontinuation, psychopathology, extrapyramidal symptoms, and treatment-emergent adverse events, were extracted. Results: A total of 9 studies involving 1416 patients that met eligibility criteria were included in the meta-analysis. No significant differences in any clinical outcomes were found between the 2 approaches (all Ps > .05). Sensitivity analyses revealed that the findings remained unchanged in the studies where switching to aripiprazole was performed or where immediate initiation of the next antipsychotic was adopted, while some significant differences were observed in switching to olanzapine or ziprasidone. Conclusions: These findings indicate that either immediate or gradual discontinuation of the current antipsychotic medication represents a viable treatment option. Clinicians are advised to choose an antipsychotic switching strategy according to individual patient needs. This said, immediate discontinuation may be advantageous both for simplicity and because a stalled cross-titration process in antipsychotic switching could end up in antipsychotic polypharmacy.

Relapse of ileus in patients with psychiatric disorders: A 2-year chart review.

OBJECTIVE: To explore risk factors for relapse of paralytic ileus in a psychiatric population. METHOD: We conducted a systematic chart-review to examine two-year relapse rates in psychiatric patients who received treatment for ileus from 2008 to 2012. Binary logistic regression analyses were performed to evaluate associations between sociodemographic and clinical characteristics and relapse of ileus. RESULTS: Sixty-three subjects (38 women; age, 66.0 ± 11.3 years) were included; 62 subjects recovered from ileus. During the subsequent 2 years, 26 (41.3%) subjects experienced relapse. In the entire sample, relapse of ileus was associated with history of abdominal surgery (P=.03, odds ratio=4.34, 95% CI=1.15-16.42) and duration of psychiatric disorders (P=.02, odds ratio=1.00, 95% CI=1.00-1.00). In a subgroup of 43 subjects with schizophrenia, history of abdominal surgery (P=.01, odds ratio=12.09, 95% CI=1.78-82.15) and age (P=.02, odds ratio=1.12, 95% CI=1.02-1.23) predicted relapse of ileus. CONCLUSIONS: Since relapse of ileus is common and can be serious in psychiatric patients, special attention is warranted to those who are old, have a history of abdominal surgery or a longer duration of psychiatric disorders to prevent relapse of ileus.

Antidepressant dose and treatment response in bipolar depression: Reanalysis of the Systematic Treatment Enhancement Program for Bipolar Disorder (STEP-BD) data.

The aim of this study is to evaluate whether an adjunct antidepressant therapy at a higher dose to a mood stabilizer would make a difference in the treatment of bipolar depression. This is a post-hoc analysis of the data from the randomized treatment for acute depression of the Systematic Treatment Enhancement Program for Bipolar Disorder (STEP-BD), in which patients with bipolar depression were randomly assigned to treatment with a mood stabilizer plus adjunctive antidepressant drugs or placebo. According to the highest dose received in the course of treatment, the subjects were divided into one of the following three groups: high-dose, low-dose and placebo groups. The primary and secondary outcomes were durable recovery (which was operationally defined as eight consecutive weeks with

Antipsychotic Polypharmacy and Corrected QT Interval: A Systematic Review.

OBJECTIVE: It remains unclear whether antipsychotic polypharmacy, a common clinical practice, is related to an increased risk of corrected time between start of Q wave and end of T wave (QTc) interval prolongation. We conducted a systematic review of the literature to address this important issue. METHOD: A systematic literature search was conducted in October 2014, using MEDLINE, Embase, and PsycINFO. Studies and case reports were included if they reported QTc intervals or QTc interval changes before and after antipsychotic polypharmacy or QTc intervals in both antipsychotic polypharmacy and monotherapy groups. RESULTS: A total of 21 articles (10 clinical trials, 4 observational studies, and 7 case reports) met inclusion criteria. The clinical trials have shown that a combination treatment with risperidone or pimozide is not obviously related to an increase in QTc interval, whereas ziprasidone or sertindole combined with clozapine may prolong QTc interval. Among the 4 observational studies, antipsychotic polypharmacy was not clearly associated with QTc prolongation in 3 studies, each cross-sectional. In contrast, one prospective study showed a significant increase in QTc interval following antipsychotic coadministration. The case reports indicated an increased risk of QTc prolongation in at least some patients receiving antipsychotic polypharmacy. CONCLUSIONS: Currently available evidence fails to confirm that antipsychotic polypharmacy worsens QTc prolongation in general, although the evidence is scarce and inconsistent. Clinicians are advised to remain conservative in resorting to antipsychotic polypharmacy, as a combination of some QTc-prolongation liable antipsychotics may further prolong QTc interval, and efficacy supporting the clinical benefits of antipsychotic polypharmacy is equivocal, at best.

Optimization of psychopharmacotherapy for schizophrenia in a male, locked, non-acute unit serving for persistently ill patients over one year.

We describe real-world psychopharmacological treatment in a Japanese, male, closed psychiatric unit where clozapie was still unavailable. Fifty-five persistently-ill patients with schizophrenia (ICD-10), mean ± S.D. age: 57.5 ± 13.0 y.o., duration of illness and admissions: 30.9 ± 15.2 years and 20.7 ± 14.5 years, respectively) treated longitudinally were evaluated. The rule was to treat with a simplest possible psychotropic regimen without polypharmacy. Compared to the baseline, the number and dose of antipsychotics were reduced from 1.9 to 1.1 and 1012 mg/day to 607 mg/day, respectively. The number of total psychotropics was minimized from 4.7 to 2.1, with a simplified once or twice daily dosing. Overall, the CGI-Severity and FACT-Sz (global functioning) improved slightly from 5.8 to 5.5 and 28.7 to 32.6, respectively. Of note, no patients got worse in comparison with the baseline clinical presentation. Forty-four patients were successfully treated with a single antipsychotic; only seven needed two antipsychotics simultaneously while 36 had been treated with antipsychotic polypharmacy at baseline. Benzodiazepines (mostly lorazepam) and antiparkinsonian drugs were prescribed in 28 and only two, respectively. Nineteen needed adjunctive valproate (average blood levels: 99.3 ± 21.8 µg/mL) and nine used lithium (0.61 ± 0.26 mEq/L). Optimization of psychopharmacotherapy is still possible for difficult-to-treat patients and, while augmentation of an antipsychotic with mood stabilizers is frequently needed, antipsychotic polypharmacy should be exceptional.

[A patient with advanced breast cancer who developed bacterial meningitis after chemotherapy].

A 76-year-old woman was admitted to our hospital because of a right breast tumor and a skin ulcer. The patient was diagnosed as having advanced breast cancer T4bN2M1(lung), Stage IV. A regimen of 5-fluorouracil(500mg/m2)with epirubicin(100mg/m / 2)and cyclophosphamide(500mg/m2)(FEC100)was administered. However, the patient was hospitalized 12 days later because of febrile neutropenia. The patient experienced a stiff neck the next day, and bacterial meningitis was diagnosed on the basis of cerebrospinal fluid examination. Antibacterial agents were administered according to the clinical practice guidelines of bacterial meningitis. The patient recovered and was discharged from our hospital 24 days after admission. Bacterial meningitis after chemotherapy is rare, but this could be progress to a serious condition. Early diagnosis and treatment are paramount in such cases.

Interventions to reduce antipsychotic polypharmacy: a systematic review.

BACKGROUND: It still remains unclear as to how to counteract antipsychotic polypharmacy that remains controversial but common. The objective of this study was to synthesize the clinical evidence to reduce antipsychotic polypharmacy (i.e. use of multiple antipsychotics) in schizophrenia. METHODS: A literature search was performed to identify clinical trials that attempted to reduce antipsychotic polypharmacy in patients with schizophrenia by any form of systematic intervention using PubMed as well as MEDLINE, EMBASE, and PsycINFO (last search: June 2012). The search terms included "antipsychotics" and "polypharmacy". Cross-referencing was also performed. RESULTS: The literature search identified 17 studies. Only 3 studies (1 randomized controlled trial and 2 open-label trials) were found that systematically switched antipsychotic polypharmacy to monotherapy. In two of them, more than two thirds of the subjects successfully completed the switch (40/58, 69.0%; 34/44, and 77.3%, respectively) while less than half the subjects tolerated it in the other study (6/14 and 42.9%) although the sample size was very small. On the other hand, 14 studies that examined impacts of interventions have physicians refrain from antipsychotic polypharmacy. While a modest intervention with educational approach alone was effective in three of the five articles, a more assertive intervention that directly cautioned physicians on the use of polypharmacy was effective in 10 of 12 articles. CONCLUSION: The literature search revealed the paucity of the data. Careful switching from polypharmacy to monotherapy seems feasible in a majority of patients with schizophrenia. Assertive interventions, rather than passive educational approaches alone, appear more effective in reducing antipsychotic polypharmacy.

Dental conditions in inpatients with schizophrenia: a large-scale multi-site survey.

BACKGROUND: Clinical relevance of dental caries is often underestimated in patients with schizophrenia. The objective of this study was to examine dental caries and to identify clinical and demographic variables associated with poor dental condition in patients with schizophrenia. METHODS: Inpatients with schizophrenia received a visual oral examination of their dental caries, using the decayed-missing-filled teeth (DMFT) index. This study was conducted in multiple sites in Japan, between October and December, 2010. A univariate general linear model was used to examine the effects of the following variables on the DMFT score: age, sex, smoking status, daily intake of sweets, dry mouth, frequency of daily tooth brushing, tremor, the Clinical Global Impression-Schizophrenia Overall severity score, and the Cumulative Illness Rating Scale for Geriatrics score. RESULTS: 523 patients were included in this study (mean ± SD age = 55.6 ± 13.4 years; 297 men). A univariate general linear model showed significant effects of age group, smoking, frequency of daily tooth brushing, and tremor (all p's < 0.001) on the DMFT score (Corrected Model: F(23, 483) = 3.55, p < 0.001, R2 = 0.42) . In other words, older age, smoking, tremor burden, and less frequent tooth brushing were associated with a greater DMFT score. CONCLUSIONS: Given that poor dental condition has been related with an increased risk of physical co-morbidities, physicians should be aware of patients' dental status, especially for aged smoking patients with schizophrenia. Furthermore, for schizophrenia patients who do not regularly brush their teeth or who exhibit tremor, it may be advisable for caregivers to encourage and help them to perform tooth brushing more frequently.