Differences in age-related characteristics among elderly patients with hip fractures.

BACKGROUND: Incidence of hip fracture among aging patients has been increasing annually in Japan; patients aged ≤74 years may be inappropriately classified as elderly. This study aimed to identify differences in the incidence of serious perioperative complications and in-hospital, 90-day, 6-month, and 1-year mortality rates according to three age groups among patients with hip fractures. METHODS: Patients aged ≥65 years treated for hip fracture by our multidisciplinary treatment system were included in this study. They were divided into the pre-old age (65-74 years), old age (75-89 years), and super-old age (≥90 years) groups. The baseline characteristics and outcomes of the three groups were compared, and variables associated with in-hospital, 30-day, 6-month, and 1-year mortality were analyzed. RESULTS: In the older population, there was a higher proportion of female participants; those with trochanteric fractures, low bone mineral density, dementia, decreased walking ability and independence in performing activities of daily living; and those not living at home. Moreover, the proportion of patients with hypertension, diabetes mellitus, and circulatory disorders, American Society of Anesthesiologists Physical Status scores, and serum albumin levels significantly differed. Further, there was a significant difference in the incidence of serious complications among males and the 6-month and 1-year mortality rates among females. In addition, female patients in the pre-old age group had a higher mortality rate at any period compared with those in the old age group. CONCLUSIONS: Patients with hip fracture who were aged 65-74, 75-89, and ≥90 years differ in terms of baseline characteristics, incidence of complications, and mortality rates. Female patients aged<75 who had fragility hip fractures potentially had worse prognosis. Our findings may be useful in preoperative explanation, postoperative management, and prognostic prediction.

The Impact of Tofogliflozin on Physiological and Hormonal Function, Serum Electrolytes, and Cardiac Diastolic Function in Elderly Japanese Patients with Type 2 Diabetes Mellitus.

The sodium glucose transporter 2 (SGLT2) inhibitor tofogliflozin is a glucose-lowering drug that causes the excretion of surplus glucose by inhibiting SGLT2. Because of tofogliflozin's osmotic diuresis mechanism, patients' serum electrolytes, body fluid levels, and cardiac function must be monitored. We retrospectively analyzed the cases of 64 elderly Japanese patients with type 2 diabetes mellitus (T2DM) who received tofogliflozin for 3 months. Their HbA1c, serum electrolytes (sodium, potassium, chloride), hematocrit, brain natriuretic peptide (cardiac volume load marker) and renin and aldosterone (RAA; an index of regulatory hormones involved in body fluid retention) were continuously monitored during the investigation period. Renal function and cardiac function (by echocardiography) were assessed throughout the period. HbA1c significantly decreased (ß1=-0.341, p<0.0001, linear regression analysis [LRA]). Most of the hormonal, electrolyte, and physiological parameters were maintained throughout the study period. In these circumstances, E/e' tended to decrease (ß1=-0.382, p=0.13, LRA). Compared to the baseline, E/e' was significantly decreased at 1 and 3 months (p<0.01, p<0.05). In the higher E/e' group (E/e'≥10, n=34), E/e' decreased significantly (ß1=-0.63, p<0.05, LRA). ΔE/e' was correlated with body-weight change during treatment (r=0.64, p<0.01). The 3-month tofogliflozin treatment improved glycemic control and diastolic function represented by E/e' in T2DM patients, without affecting serum electrolytes, renal function, or RAA. No negative impacts on the patients were observed. Three-month tofogliflozin treatment lowered glucose and improved cardiac diastolic function.

Postoperative Urinary Retention in Japanese Elderly Males with a Femoral Neck or Trochanteric Fracture.

We assessed risk factors for postoperative urinary retention (UR) in elderly males with femoral bone fractures: 169 Japanese males (mean age 81.95 ± 1.19 years) who had undergone hip surgery at a municipal hospital (Toyama, Japan). A multiple logistic regression analysis was used to test possible risk factors for UR: age, body mass index, serum albumin, cognitive impairment, activities of daily living (ADL), and history of diabetes mellitus (DM). UR occurred in 24 (14.2%) of the 169 patients. A multivariate logistic regression analysis with age adjustment showed that ADL (odds ratio [OR] 3.88; 95% confidence interval [CI]: 1.2-12.5, p=0.023) was significantly associated with the development of UR, and a history of DM showed marginal significance for UR occurrence (OR 0.36, 95%CI: 0.11-10, p=0.064). These results suggests that ADL is a risk factor for UR development in elderly males who have undergone surgery for femoral neck or trochanter fractures.

Orthogeriatric co-management at a regional core hospital as a new multidisciplinary approach in Japanese hip fracture operation.

BACKGROUND: This study aimed to evaluate the effects of orthogeriatric co-management of hip fractures at a regional core hospital. METHODS: This study included patients with proximal hip fracture. Patients were divided into two groups, conventional multidisciplinary group I including patients attending the hospital between April 2015 and March 2016 and orthogeriatric group II including patients attending the hospital between April 2016 and March 2017, which were compared etrospectively. In the control group, the conventional multidisciplinary team treated patients as whole-body controls. In the intervention group, the newly recruited geriatricians performed physical examinations, laboratory tests, radioactive imaging, and physiological tests. Furthermore, they consulted ward pharmacists, rigorously conducted positive polypharmacy interventions , and evaluated the type and number of mediated drugs on admission. RESULTS: The number of medicated drugs significantly decreased from 6.03 ± 4.3 on admission to 5.50 ± 3.59 on discharge in group II, whereas group I did not show a significant decrease. Despite the more number of hospitalized patients in group II (166 patients) than in group I (126 patients), the recovery rate from postoperative urinary retention increased significantly from 57.8% (19/30) in group I to 84.3% (32/59) in group II (p = 0.049), while the incidence of aspiration pneumonia decreased from 7.1% (9/126) in group I to 2.49% (4/166) in group II (p = 0.08). The patients received six or more prescribed drugs on admission, and the number remained constant. However, the number of medicated drugs on discharge showed a marginally significant decrease from 6.03 ± 4.3 in group I to 5.50 ± 3.59 in group II (p < 0.05). CONCLUSIONS: Compared to the conventional multidisciplinary group, the orthogeriatric team contributed to reducing the number of multi-effect drugs and perioperative complications without negatively affecting mortality despite the increased number of patients. The in-hospital mortality rate did not change between the groups. The orthogeriatric program succeeded in preventing and treating perioperative complications.

Multidisciplinary care model for geriatric patients with hip fracture in Japan: 5-year experience.

INTRODUCTION: Japan is a super-aging society, the geriatric care system establishment for hip fractures is at an urgent task. This report described our concept of multidisciplinary care model for geriatric hip fractures and 5-year outcomes at the Toyama City Hospital, Japan. METHODS: In this retrospective cohort study, a multidisciplinary treatment approach was applied for elderly patients with hip fracture since 2014. These patients (n = 678, males: n = 143, mean age: 84.6 ± 7.5 years), were treated per the multidisciplinary care model. Time to surgery, length of hospital stays, complications, osteoporosis treatment, mortality, and medical costs were evaluated. RESULTS: The mean time to surgery was 1.7 days. Overall, 78.0% patients underwent surgery within 2 days. The mean duration of hospital stay was 21.0 ± 12.4 days. The most frequent complication was deep venous thrombosis (19.0%) followed by dysuria (14.5%). Severe complications were pneumonia 3.4%, heart failure 0.8% and pulmonary embolism 0.4%. The in-hospital mortality rate was 1.2%. The 90-day, 6-month, and 1-year mortality rates were 2.5%, 6.7%, and 12.6%, respectively. The pharmacotherapy rate for osteoporosis at discharge was 90.7%, and the continuation pharmacotherapy rate was 84.7% at 1-year follow-up. The total hospitalization medical cost per person was lower than about 400 other hospitals' average costs every year, totaled 14% less during the 5-year study period. CONCLUSION: We have organized a multidisciplinary team approach for geriatric hip fracture. This approach resulted in a shorter time to surgery and hospital stay than the national average. The incidence of severe complications and mortality was low. The multidisciplinary treatment has maintained a high rate of osteoporosis treatment after discharge and at follow-up. Furthermore, the total medical cost per person was less than the national average. Thus, the multidisciplinary treatment approach for geriatric hip fractures was effective and feasible to conduct in Japan.

A PERIOD3 variant causes a circadian phenotype and is associated with a seasonal mood trait.

In humans, the connection between sleep and mood has long been recognized, although direct molecular evidence is lacking. We identified two rare variants in the circadian clock gene PERIOD3 (PER3-P415A/H417R) in humans with familial advanced sleep phase accompanied by higher Beck Depression Inventory and seasonality scores. hPER3-P415A/H417R transgenic mice showed an altered circadian period under constant light and exhibited phase shifts of the sleep-wake cycle in a short light period (photoperiod) paradigm. Molecular characterization revealed that the rare variants destabilized PER3 and failed to stabilize PERIOD1/2 proteins, which play critical roles in circadian timing. Although hPER3-P415A/H417R-Tg mice showed a mild depression-like phenotype, Per3 knockout mice demonstrated consistent depression-like behavior, particularly when studied under a short photoperiod, supporting a possible role for PER3 in mood regulation. These findings suggest that PER3 may be a nexus for sleep and mood regulation while fine-tuning these processes to adapt to seasonal changes.

Procalcitonin, brain natriuretic peptide and albumin as markers to predict prognosis in hospitalized older Japanese patients with a risk of infection.

AIM: Whether serum concentration of procalcitonin (PCT), brain natriuretic peptide (BNP) and albumin (Alb) have an association with the outcome of hospitalized older patients is unclear. We investigated clinical outcomes and any predictive factors in hospitalized Japanese older patients with a risk of infection. METHODS: In the retrospective study, 820 Japanese patients were followed up for 30 days or until death. During the observation period, 656 patients survived and 164 patients died. The predictive factors of death were analyzed according to demographic and clinical variables. RESULTS: The survival rate was decreased as the serum PCT increased from <0.5 to ≥10 ng/mL, as was also the case with BNP from <300 to ≥300 pg./mL, whereas low Alb (<2.5 g/dL) showed a lower survival rate than high Alb (≥2.5 g/dL; P < 0.01). Using the Cox regression model, the multivariable-adjusted hazard ratios (95% confidence interval) were as follows: PCT 0.5-2 versus <0.5 ng/mL: 1.61(1.04-2.49), PCT 2-10 versus <0.5 ng/mL: 1.91(1.15-3.16), PCT ≥10 versus <0.5 ng/mL: 2.90(1.84-4.59), high BNP 1.26 (0.89-1.76) and low Alb 0.68 (0.52-0.87). The mortality rate increased as the number of scores (PCT + BNP + Alb) increased. CONCLUSIONS: Concentration-dependent high PCT, high BNP and low Alb were positive risk factors associated with poor prognosis in hospitalized older patients with a risk of infection. Geriatr Gerontol Int 2024; 24: 571-576.

The combination of the low immunohistochemical expression of peroxiredoxin 4 and perilipin 2 predicts longer survival in pancreatic ductal adenocarcinoma with peroxiredoxin 4 possibly playing a main role.

Pancreatic ductal adenocarcinoma (PDAC) is a fatal disease with poor prognosis. Therefore, indicators that can be used for the early prediction of the prognosis of PDAC are needed. Peroxiredoxin (PRDX) 4 is a secretion-type antioxidant enzyme located in the cytoplasmic endoplasmic reticulum. Recent studies have reported that it is closely related to the development and prognosis of many types of cancer. Perilipin (PLIN) 2 is a lipid droplet coating protein. The high expression of PLIN2 is known to be an indicator of some types of cancer and oxidative stress management. It is highly suggestive of the interplay between PRDX4 and PLIN2 to some degree. In this study, we collected 101 patients' clinical data and paraffin-embedded specimens with PDAC and analyzed them with immunohistochemical staining of PRDX4 and PLIN2. We found that the low expression of PRDX4 predicts longer survival and a better clinical condition in PDAC patients. Moreover, when the low expression of PRDX4 is combined with the low expression of PLIN2, the 3-year survival is significantly improved. Univariate and multivariate Cox proportional hazard analyses showed that the PRDX4 expression in PDAC was an independent prognostic factor for survival. Taken together, between PRDX4 and PLIN2, PRDX4 plays a main role in prognosis and has the potential to become a clinical prognostic indicator of PDAC.

[Vitamin D in relation to frailty and locomotive syndrome].

Frailty is an extremely common and serious health problem in the elderly. Frailty has been described as "a biologic syndrome of decreased reserve and resistance to stressors, resulting from cumulative declines across multiple physiologic systems and causing vulnerability to adverse health outcomes" by Fried and colleagues. Frailty is associated with incident falls, functional limitation, disability, and mortality. There are many reports that vitamin D deficiency may play roles in diabetes mellitus, cancers, multiple sclerosis, and other autoimmune diseases, and was associated with poorer physical performance, falls and fractures, and a greater risk of nursing home admission. Recently, researches suggest that vitamin D may provide treatment and prevention from these diseases lead to frailty. Vitamin D is expected to be a treatment for frailty in an aging society.

A new predictive tool consolidating CURB-65 with procalcitonin and albumin to assess short-term mortality in hospitalized elderly patients with infectious disease: A retrospective study of a patient cohort.

BACKGROUND: Hospitalized elderly patients are often at risk of life-threatening infectious diseases such as pneumonia and urinary tract infection, thus diagnostic tools for bacterial infections are demanded. We developed a new predictive tool consolidating modified CURB-65, procalcitonin (PCT) and albumin (Alb). METHOD: This is a retrospective study. Modified CURB-65 (mCURB-65) score, PCT, Alb, and various cardiovascular/respiratory/renal functions were measured. Survival analyses were conducted to assess 30-days mortality of elderly patients using mCURB-65 score, PCT and Alb. The consolidated scores were compared with the number of patients died. RESULTS: There were 445 elderly patients included. Kaplan-Meier survival curves showed significant differences between the high and low groups of mCURB-65, PCT and Alb (log-rank test, P < .001). Cox proportional regression showed that the hazard ratios (95% confidence intervals) for high mCURB-65, high Alb, and high PCT were all significant, 1.95 (1.24-3.05), 0.50 (0.32-0.77), and 2.09 (1.32-3.31), respectively. The consolidated scores showed tendency of increase with proportion of the number of patients died. CONCLUSIONS: The consolidated score consisted of mCURB-65, PCT and Alb can be a useful tool to predict short-term mortality of the hospitalized elderly patients with infectious disease.

[Frontiers in vitamin D; basic research and clinical application. Activated vitamin D in psoriasis].

Psoriasis is a chronic immune-mediated disease that appears on the skin. It occurs when the immune system sends out faulty signals that speed up the growth cycle of skin cells. Psoriasis is typically a lifelong condition. There is currently no cure, but various treatments can help to control the symptoms. Activated vitamin D3 is the first-line treatment for psoriasis. Psoriasis is often treated with combination therapy of activated vitamin D3 and other treatment. Depending on the severity and location of outbreaks, individuals may experience significant physical discomfort and some disability. Thus, the goal for the treatment of psoriasis is to control the signs and symptoms over a long period and to ameliorate the quality of life of psoriasis patients.

Tocilizumab and PMX-DHP have efficacy for severe COVID-19 pneumonia.

In coronavirus disease 2019 pneumonia, a cytokine storm resulting from an excessive inflammatory response to the viral infection is thought to play a role in the exacerbation of the pneumonia and its prognosis. Favipiravir and ciclesonide are not effective in the inhibition of the cytokine storm. In this case report, we describe the experience of tocilizumab administration and polymyxin B immobilized fiber direct hemoperfusion in severe coronavirus disease 2019 pneumonia patient. A 52-year-old man presented with fever and dyspnea and was diagnosed with coronavirus disease 2019 pneumonia based on a polymerase chain reaction test. Mechanical ventilation and favipiravir administration were started for respiratory failure. However, favipiravir could not be continued due to hepatic dysfunction. Consequently, tocilizumab was administered, and continuous hemodiafiltration and endotoxin adsorption therapy (polymyxin B immobilized fiber direct hemoperfusion) were performed for acute renal failure. C-reactive protein decreased from 44 to 3.52 mg/dL, and the patient's respiratory status improved over time, enabling mechanical ventilation to be withdrawn. This case indicates that adding polymyxin B immobilized fiber direct hemoperfusion to tocilizumab administration may further increase efficacy in coronavirus disease 2019 treatment; however, more case-control studies are needed.

Correction to: Relationship Between Blood Pressure Levels on Admission and the Onset of Acute Pneumonia in Elderly Patients With Cerebral Hemorrhage.

[This corrects the article DOI: 10.14740/jocmr4330.].

Examination of Endoscopic Ultrasonographic Diagnosis for the Depth of Early Gastric Cancer.

BACKGROUND: Endoscopic ultrasonography (EUS) is one of the helpful tools to diagnose depth of early gastric cancer (EGC). In this study, we examined efficiencies of EUS for EGC such as overall accuracy, risk factors of over/under-staging, and accuracies of each invasive distance. METHODS: A total of 403 EGC lesions that could be investigated by EUS during pre-operation and histological diagnosis after endoscopic submucosal dissection (ESD) or surgery were enrolled in this study. For the 403 cases, we analyzed the accuracies of depth by conventional endoscopy (CE) and EUS retrospectively. We evaluated the clinical survey items of CE and EUS which will be described later to compare the differences between "accuracy group" and "over-staging group", and between "accuracy group" and "under-staging group", retrospectively. Additionally, 78 EGC lesions which were confined to the submucosa and for which it was possible to measure accurate invasive distance from the muscularis mucosae were examined for the relationship between preoperative diagnosis of depth by CE and EUS and invasive distance retrospectively. RESULTS: The overall accuracies of both CE and EUS in predicting EGC invasion depth were 87.3%. For CE staging, histological classification was the factor which influenced over-staging. Gastric regions and tumor area were the factors which influenced under-staging of CE. For EUS staging, tumor area was the factor which influenced over-staging, and gastric regions were the factors which influenced under-staging. Both CE and EUS were not sufficient for predicting the lesions confined to < 500 µm from the muscularis mucosae because the accuracies of both in predicting depth were less than 50%. However, EUS has a higher accuracy than CE for the lesions confined to 500 - 2,000 µm. CONCLUSIONS: The overall accuracies of both CE and EUS in predicting EGC invasion depth were equal, but the contributing factors for over/under-staging were different. Both CE and EUS are not sufficient at present to predict the lesions confined to < 500 µm from the muscularis mucosae. However, the accuracy of EUS in predicting them may increase if high-performance EUS systems are developed in the future.

A Case of Refractory Esophageal Ulcer Caused by Radiotherapy for Hepatocellular Carcinoma.

A 77-year-old man who underwent radiotherapy for hepatocellular carcinoma 6 months prior consulted for esophageal obstruction. Esophagogastroduodenoscopy revealed an esophageal ulcer caused by radiotherapy for hepatocellular carcinoma. He was treated with dietary counseling and vonoprazan. After 9 months, the ulcer improved but a moderate stenosis remained. Several factors such as high fraction size, history of chemotherapy, and stress associated with food intake might involve in the development of a radiation-associated ulcer. Opportunities to choose radiotherapy for hepatocellular carcinoma may increase, so we hypothesize that esophageal ulcers might be a complication that should be noted associated with this therapy.

Effects of tofogliflozin on adrenocorticotropic hormone, renin and aldosterone, and cortisol levels in elderly patients with diabetes mellitus: A retrospective study of a patient cohort.

ABSTRACT: Adrenocorticotropic hormone (ACTH) and cortisol reportedly play a role in glycemic control in patients with type 2 diabetes mellitus (T2DM); however, the underlying mechanism remains controversial. We retrospectively investigated the effect of tofogliflozin on serum ACTH and cortisol levels in elderly patients with T2DM.Patients received 20 mg tofogliflozin daily for 3 months. Serum ACTH and cortisol levels were measured at baseline, as well as after 1 month and 3 months of tofogliflozin therapy.Serum ACTH levels were significantly reduced 3 months after tofogliflozin treatment (P < .01). Additionally, serum cortisol levels were reduced 3 months after tofogliflozin treatment, demonstrating borderline significance (P = .05). The higher body mass index (BMI; ≥25 kg/m2) group showed higher ACTH and cortisol levels than the lower BMI (<25 kg/m2) group, with borderline significance (P = .05). Renin levels were significantly increased 1 month after treatment (P < .05), maintaining serum aldosterone levels in parallel with the extracellular fluid.Our findings suggested that tofogliflozin decreased both serum ACTH and cortisol levels, with higher levels observed in the high BMI group. Tofogliflozin increased serum renin levels while maintaining serum aldosterone and extracellular fluid levels. Collectively, tofogliflozin could affect the hypothalamic-pituitary-adrenal pathway in patients with T2DM, especially in the low BMI group.

Effects of paraxanthine and caffeine on sleep, locomotor activity, and body temperature in orexin/ataxin-3 transgenic narcoleptic mice.

STUDY OBJECTIVE: Caffeine, an adenosine A1 and A2a receptor antagonist, is a widely consumed stimulant and also used for the treatment of hypersomnia; however, the wake-promoting potency of caffeine is often not strong enough, and high doses may induce side effects. Caffeine is metabolized to paraxanthine, theobromine, and theophylline. Paraxanthine is a central nervous stimulant and exhibits higher potency at A1 and A2 receptors, but has lower toxicity and lesser anxiogenic effects than caffeine. DESIGN: We evaluated the wake-promoting efficacy of paraxanthine, caffeine, and a reference wake-promoting compound, modafinil, in a mice model of narcolepsy, a prototypical disease model of hypersomnia. Orexin/ataxin-3 transgenic (TG) and wild-type (WT) mice were subjected to oral administration (at ZT 2 and ZT14) of 3 doses of paraxanthine, caffeine, modafinil, or vehicle. RESULTS: Paraxanthine, caffeine, and modafinil significantly promoted wakefulness in both WT and narcoleptic TG mice and proportionally reduced NREM and REM sleep in both genotypes. The wake-promoting potency of 100 mg/kg p.o. of paraxanthine during the light period administration roughly corresponds to that of 200 mg/kg p.o. of modafinil. The wake-promoting potency of paraxanthine is greater and longer lasting than that of the equimolar concentration of caffeine, when the drugs were administered during the light period. The wake-promotion by paraxanthine, caffeine, and modafinil are associated with an increase in locomotor activity and body temperature. However, the higher doses of caffeine and modafinil, but not paraxanthine, induced hypothermia and reduced locomotor activity, thereby confirming the lower toxicity of paraxanthine. Behavioral evaluations of anxiety levels in WT mice revealed that paraxanthine induced less anxiety than caffeine did. CONCLUSIONS: Because it is also reported to provide neuroprotection, paraxanthine may be a better wake-promoting agent for hypersomnia associated with neurodegenerative diseases.

Emerging treatments for narcolepsy and its related disorders.

IMPORTANCE OF THE FIELD: Narcolepsy is a chronic sleep disorder, characterized by excessive daytime sleepiness (EDS), cataplexy, hypnagogic hallucinations, sleep paralysis and nocturnal sleep disruption. Non-pharmacological treatments (i.e., behavioral modification) are often helpful for the clinical management of narcoleptic patients. As these symptoms are often disabling, most patients need life-long treatments. Over 90% of diagnosed narcoleptic patients are currently prescribed medications to control their symptoms; however, available treatments are merely symptomatic. AREAS COVERED IN THIS REVIEW: This review presents a description of the clinical symptoms of narcolepsy, followed by a discussion of the state-of-the-art knowledge regarding the disorder and related emerging treatments. In preparing this review, an extensive literature search was conducted using Pubmed. Only selected references from 1970 to 2008 are cited. WHAT THE READER WILL GAIN: This review focuses on emerging treatments for human narcolepsy, and the reader will gain significant knowledge of current and future treatment for this and related disorders. Traditionally, amphetamine-like stimulants (i.e., dopaminergic release enhancers) have been used for clinical management to improve EDS, and tricyclic antidepressants have been used as anticataplectics. However, treatments have recently evolved which utilize better tolerated compounds, such as modafinil (for EDS) and adrenergic/serotonergic selective reuptake inhibitors (as anticataplectics). In addition, night time administration of a short-acting sedative, gamma-hydroxybutyrate, has been used for the treatment for EDS and cataplexy. As a large majority of human narcolepsy is hypocretin peptide deficient, hypocretin replacement therapy may also be a new therapeutic option; yet, this option is still unavailable. In addition to the hypocretin-based therapy, a series of new treatments are currently being tested in animal and/or humans models. These potential options include novel stimulant and anticataplectic drugs as well as immunotherapy, based on current knowledge of the pathophysiology of narcolepsy with cataplexy. TAKE HOME MESSAGE: We expect that more pathophysiology-based treatments, capable of curing and/or preventing narcolepsy and related diseases, will be available in near future. As cases of EDS, associated with other neurological conditions (i.e., symptomatic narcolepsy or narcolepsy due to medical conditions), are often linked with hypocretin deficiency, these novel therapeutic options may also be applied to treatment of these disabling conditions.

Hypocretin ligand deficiency in narcolepsy: recent basic and clinical insights.

Narcolepsy is a chronic sleep disorder characterized by excessive daytime sleepiness, cataplexy, hypnagogic hallucinations, and sleep paralysis. Both sporadic and familial forms exist in humans. Recently, the major pathophysiology of human narcolepsy was indicated, based on discovery, through animal study, of narcolepsy genes involved in the pathology of hypocretin/orexin ligand and its receptor. Hypocretin ligand deficiency is found in most patients with narcolepsy with cataplexy. This deficiency likely is the result of postnatal cell death of hypocretin neurons, and involvement of autoimmune mechanisms is suggested. Hypocretin deficiency also is found in symptomatic narcolepsy and excessive daytime sleepiness with neurologic conditions, including immune-mediated neurologic disorders. These findings have significant clinical relevance and promote understanding of hypocretin cell death mechanisms. Already, discoveries in humans have led to a new diagnostic test for narcolepsy. Currently, hypocretin replacement therapy has emerged as a promising therapeutic option, and experiments using gene therapy and cell transplantation are in progress.

Mortality and the Risk Factors in Elderly Female Patients With Femoral Neck and Trochanteric Fractures.

BACKGROUND: The main purpose of this study is to exhaustively explore risk factors, including age, gender, and several clinical indices, for mortality in elderly patients with femoral neck fracture and to evaluate some of them using survival analyses. METHODS: This was a retrospective study tracking 1 year for vital prognosis. Data were collected at post-operation from medical records of the cases. Survival analysis was conducted to investigate the risk factors for death, including albumin, urinary retention, activity of daily living (ADL), and cognitive disorder. RESULTS: We recruited 318 patients with a history of hip surgery carried out at Toyama Municipal Hospital, in which 39 patients died for 1 year after discharge. The results showed a significant decrease in survival rate in low albumin, positive urinary retention, and low ADL (P < 0.01, by log-rank test). The hazard ratios (95% confidence interval) of albumin, urinary retention, ADL, and cognitive disorder were 0.36 (0.19 - 0.69), 0.4 (0.2 - 0.8), 0.29 (0.15 - 0.58) and 0.65 (0.32 - 1.29), respectively. CONCLUSIONS: This study demonstrated that albumin, urinary retention and ADL were the important risk factors for mortality, and suggested that the postoperative management of albumin, urinary retention and ADL is important, especially in elderly female patients receiving surgery of femoral neck and trochanteric fractures.