Treatment of spinal cord injury with biomaterials and stem cell therapy in non-human primates and humans

Spinal cord injury results in the loss of sensory,motor,and autonomic functions,which almost always produces permanent physical disability.Thus,in the search for more effective treatments than those already applied for years,which are not entirely efficient,researches have been able to demonstrate the potential of biological strategies using biomaterials to tissue manufacturing through bioengineering and stem cell therapy as a neuroregenerative approach,seeking to promote neuronal recovery after spinal cord injury.Each of these strategies has been developed and meticulously evaluated in several animal models with the aim of analyzing the potential of interventions for neuronal repair and,consequently,boosting functional recovery.Although the majority of experimental research has been conducted in rodents,there is increasing recognition of the importance,and need,of evaluating the safety and efficacy of these interventions in non-human primates before moving to clinical trials involving therapies potentially promising in humans.This article is a literature review from databases(PubMed,Science Direct,Elsevier,Scielo,Redalyc,Cochrane,and NCBI)from 10 years ago to date,using keywords(spinal cord injury,cell therapy,non-human primates,humans,and bioengineering in spinal cord injury).From 110 retrieved articles,after two selection rounds based on inclusion and exclusion criteria,21 articles were analyzed.Thus,this review arises from the need to recognize the experimental therapeutic advances applied in non-human primates and even humans,aimed at deepening these strategies and identifying the advantages and influence of the results on extrapolation for clinical applicability in humans.

Imperative for long-term management and surveillance in Kawasaki disease

Kawasaki disease(KD)is a significant pediatric vasculitis known for its potential to cause severe coronary artery complications.Despite the effectiveness of initial treatments,such as intravenous immunoglobulin,KD patients can experience long-term cardiovascular issues,as evidenced by a recent case report of an adult who suffered a ST-segment elevation myocardial infarction due to previous KD in the World Journal of Clinical Cases.This editorial emphasizes the critical need for long-term management and regular surveillance to prevent such complications.By drawing on recent research and case studies,we advocate for a structured approach to follow-up care that includes routine cardiac evaluations and preventive measures.

Optimizing care for gastric cancer with overt bleeding:Is systemic therapy a valid option?

Gastric cancer(GC)and gastroesophageal junction cancer(GEJC)represent a significant burden globally,with complications such as overt bleeding(OB)further exacerbating patient outcomes.A recent study by Yao et al evaluated the effectiveness and safety of systematic treatment in GC/GEJC patients presenting with OB.Using propensity score matching,the study balanced the comparison groups to investigate overall survival and treatment-related adverse events.The study's findings emphasize that systematic therapy can be safe and effective and contribute to the ongoing debate about the management of advanced GC/GEJC with OB,highlighting the complexities of treatment decisions in these high-risk patients.

Human induced pluripotent stem cell-derived therapies for regeneration after central nervous system injury

In recent years,the progression of stem cell therapies has shown great promise in advancing the nascent field of regenerative medicine.Considering the non-regenerative nature of the mature central nervous system,the concept that“blank”cells could be reprogrammed and functionally integrated into host neural networks remained intriguing.Previous work has also demonstrated the ability of such cells to stimulate intrinsic growth programs in post-mitotic cells,such as neurons.While embryonic stem cells demonstrated great potential in treating central nervous system pathologies,ethical and technical concerns remained.These barriers,along with the clear necessity for this type of treatment,ultimately prompted the advent of induced pluripotent stem cells.The advantage of pluripotent cells in central nervous system regeneration is multifaceted,permitting differentiation into neural stem cells,neural progenitor cells,glia,and various neuronal subpopulations.The precise spatiotemporal application of extrinsic growth factors in vitro,in addition to microenvironmental signaling in vivo,influences the efficiency of this directed differentiation.While the pluri-or multipotency of these cells is appealing,it also poses the risk of unregulated differentiation and teratoma formation.Cells of the neuroectodermal lineage,such as neuronal subpopulations and glia,have been explored with varying degrees of success.Although the risk of cancer or teratoma formation is greatly reduced,each subpopulation varies in effectiveness and is influenced by a myriad of factors,such as the timing of the transplant,pathology type,and the ratio of accompanying progenitor cells.Furthermore,successful transplantation requires innovative approaches to develop delivery vectors that can mitigate cell death and support integration.Lastly,host immune responses to allogeneic grafts must be thoroughly characterized and further developed to reduce the need for immunosuppression.Translation to a clinical setting will involve careful consideration when assessing both physiologic and functional outcomes.This review will highlight both successes and challenges faced when using human induced pluripotent stem cell-derived cell transplantation therapies to promote endogenous regeneration.

Long-term efficacy of perioperative chemoradiotherapy on esophageal squamous cell carcinoma

AIM: To investigate the role of perioperative chemoradiotherapy (CRT) in the treatment of locally advanced thoracic esophageal squamous cell carcinoma (ESCC). METHODS: Using preoperative computed tomography (CT)-based staging criteria, 238 patients with ESCC (stage ⅡⅢ ) were enrolled in this prospective study between January 1997 and June 2004. With informed consent, patients were randomized into 3 groups: preoperative CRT (80 cases), postoperative CRT (78 cases) and surgery alone (S) (80 cases). The 1-, 3-, 5and 10-year survival were followed up. Progressionfree survival (PFS) was chosen as the primary endpoint by treatment arm measured from study entry until documented progression of disease or death from any cause. The secondary endpoint was overall survival (OS) determined as the time (in months) between the date of therapy and the date of death. Other objectives were surgical and adjuvant therapy complications.RESULTS: With median follow-up of 45 mo for all the enrolled patients, significant differences in the 1-, 3-, 5-, 10-year OS (91.3%, 63.5%, 43.5%, 24.5% vs 91%, 62.8%, 42.3%, 24.4% vs 87.5%, 51.3%, 33.8%, 12.5%, P = 0.0176) and PFS (89.3%, 61.3%, 37.5%, 18.1% vs 89.1%, 61.1%, 37.2%, 17.8% vs 84.5%, 49.3%, 25.9%, 6.2%, P = 0.0151) were detected among the 3 arms. There were no significant differences in OS and PFS between the preoperative CRT and postoperative CRT arm (P > 0.05). For the patients who had radical resection, significant differences in median PFS (48 mo vs 61 mo vs 39.5 mo, P = 0.0331) and median OS (56.5 mo vs 72 mo vs 41.5 mo, P = 0.0153) were detected among the 3 arms, but there were no significant differences in OS and PFS between the preoperative CRT and postoperative CRT arm (P > 0.05). The local recurrence rates in the preoperative CRT, postoperative CRT group and S group were 11.3%, 14.1% and 35%, respectively (P < 0.05). No significant differences were detected among the 3 groups when comparing complications but tended to be in favor of the postoperative CRT and S groups (P > 0.05). Toxicities of CRT in the preoperative or postoperative CRT arms were mostly moderate, and could be quickly alleviated by adequate therapy. CONCLUSION: Rational application of preoperative or postoperative CRT can provide a benefit in PFS and OS in patients with locally advanced ESCC.

Oncological results, functional outcomes and health-related quality-of-life in men who received a radical prostatectomy or external beam radiation therapy for localized prostate cancer： a study on long-term patient outcome with risk stratification

Health-related quality-of-life （HRQOL） after a radical prostatectomy （RP） or extemal beam radiation therapy （EBRT） has not been studied in conjunction with oncological outcomes in relation to disease risk stratification. Moreover, the long-term outcomes of these treatment approaches have not been studied. We retrospectively analyzed oncological outcomes between consecutive patients receiving RP （n = 86） and EBRT （n = 76） for localized prostate cancer. HRQOL and functional outcomes could be assessed in 62 RP （79%） and 54 EBRT （79%） patients over a 3-year follow-up period （median： 41 months） using the Medical Outcomes Study Short Form-36 （SF-36） and the University of Califomia Los Angeles Prostate Cancer Index （UCLA PCI）. The 5-year biochemical progression-free survival did not differ between the RP and EBRT groups for low-risk （74.6% vs. 75.0%, P = 0.931） and intermediate-risk （61.3% vs. 71.1%, P = 0.691） patients. For high-risk patients, progression-free survival was lower in the RP group （45.1%） than in the EBRT group （79.7%） （P = 0.002）. The general HRQOL was comparable between the two groups. Regarding functional outcomes, the RP group reported lower scores on urinary function and less urinary bother and sexual bother than the EBRT group （P 〈 0.001, P 〈 0.05 and P 〈 0.001, respectively）. With risk stratification, the low- and intermediate-risk patients in the RP group reported poorer urinary function than patients in the EBRT group （P 〈 0.001 for each）. The sexual function of the high-risk patients in the EBRT group was better than that of the same risk RP patients （P 〈 0.001）. Biochemical recurrence was not associated with the UCLA PCI score in either group. In conclusion, low- to intermediate-risk patients treated with an RP may report relatively decreased urinary function during long-term follow-up. The patient＇s HRQOL after treatment did not depend on biochemical recurrence.

Long-term outcomes of a phase Ⅱ randomized controlled trial comparing intensity-modulated radiotherapy with or without weekly cisplatin for the treatment of locally recurrent nasopharyngeal carcinoma

Background:Salvage treatment for locally recurrent nasopharyngeal carcinoma(NPC) is complicated and relatively limited.Radiotherapy,combined with effective concomitant chemotherapy,may improve clinical treatment outcomes.We conducted a phase Ⅱ randomized controlled trial to evaluate the efficacy of intensity-modulated radiotherapy with concomitant weekly cisplatin on locally recurrent NPC.Methods:Between April 2002 and January 2008,69 patients diagnosed with non-metastatic locally recurrent NPC were randomly assigned to either concomitant chemoradiotherapy group(n = 34) or radiotherapy alone group(n = 35).All patients received intensity-modulated radiotherapy.The radiotherapy dose for both groups was 60 Gy in 27 fractions for 37 days(range 23-53 days).The concomitant chemotherapy schedule was cisplatin 30 mg/m^2 by intravenous infusion weekly during radiotherapy.Results:The median follow-up period of all patients was 35 months(range 2-112 months).Between concomitant chemoradiotherapy and radiotherapy groups,there was only significant difference in the 3-year and 5-year overall survival(OS) rates(68.7%vs.42.2%,P = 0.016 and 41.8%vs.27.5%,P = 0.049,respectively).Subgroup analysis showed that concomitant chemoradiotherapy significantly improved the 5-year OS rate especially for patients in stage rT3-4(33.0%vs.13.2%,P = 0.009),stages Ⅲ-Ⅳ(34.3%vs.13.2%,P = 0.006),recurrence interval >30 months(49.0%vs.20.6%,P = 0.017),and tumor volume >26 cm^3(37.6%vs.0%,P = 0.006).Conclusion:Compared with radiotherapy alone,concomitant chemoradiotherapy can improve OS of the patients with locally recurrent NPC,especially those with advanced T category(rT3-4) and stage(lll-IV) diseases,recurrence intervals >30 months,and tumor volume >26 cm^3.

EVALUATION OF NEUROPROTECTIVE EFFECTS OF LONG-TERM LOW DOSE HORMONE REPLACEMENT THERAPY ON POSTMENOPAUSAL WO-MEN BRAIN HIPPOCAMPUS USING MAGNETIC RESONANCE SCANNER

To investigate the effects of long-term low dose hormone replacement therapy （HRT） on postmenopaosal women in homone level, cognition score, hippocampus volume, and magnetic resonance spectroscopy （MRS） parameters. Methods A total of 182 postmenopausal women aged 50-87 years were chosen at Peking Union Medical College Hospital and assigned to HRT group and control group. The volunteers of HRT group had taken low dose hormone [ estradiol （E2 ） 0. 5-1.0 mg and progesterone 0.5-2.0 mg, once a day ] for 4-33 years. The concentrations of E2, progesterone, and testosterone were measured using enzyme-linked immunosorbent assay （ELISA）. The gene types of apolipoprotein E （ApoE） were measured by polymerase chain reaction, and the subjects with susceptible genes （ ApoE ε3/ε4） of Alzheimer＇s disease （AD） were screened. Their hippocampus volumes and MRS parameters were obtained through magnetic resonance imaging （MRI）, and results in two groups were analyzed by statistical method. Results Compared with control group, the concentrations of E2 at each age stage in HRT group were significantly higher （P 〈0. 05） except the 80-89 years old subgroup; yet, there were no statistical differences in the concentrations of progesterone and testosterone between the two groups. There was no obvious difference in ApoE subtypes distribution between the two groups The results of hippocampus MRI for the subjects with susceptible genes ApoE ε3/ε4 （HRT group 14 cases, control group 11 cases） showed that the ratio of bilateral hippocampus volume to whole brain volume in HRT group （0. 406 ± 0.028） was signiticantlyhigher than control gronp （0.369±0.031, P〈0.05）. Theresults of ^1H MRS for the subjects with susceptible genes ApoE ε3/ε4 （ HRT group 12 cases, control group 11 cases） showed that the N-acetylaspartate/total creatine at the area of hippocampus in HRT group （ 1.54±0. 08 ） were significantly higher than control group （ 1.45±0. 13, P 〈 0. 05）. Conclusions For postmenopausal women, long-term low dose HRT can maintain the physiological concentration of E2 in plasma. Furthermore, the hippocampus MRI performed on those with ApoE ε3/ε3 genes shows that long-term low dose HRT can prevent hippocampus atrophy, which is beneficial to maintain the brain function and prevent AD.

Neoadjuvant therapy for pancreas cancer: Past lessons and future therapies

Pancreatic adenocarcinoma remains a most deadly malignancy, with an overall 5-year survival of 5%. A subset of patients will be diagnosed with potentially resectable disease, and while complete surgical resection provides the only chance at cure, data from trials of postoperative chemoradiation and/or chemotherapy demonstrate a modest survival advantage over those patients who undergo resection alone. As such, most practitioners believe that completion of multimodality therapy is the optimal treatment. However, the sequence of surgery, chemotherapy and radiation therapy is frequently debated, as patients may benefit from a neoadjuvant approach by initiating chemotherapy and/or chemoradiation prior to resection. Here we review the rationale for neoadjuvant therapy, which includes a higher rate of completion of multimodality therapy, minimizing the risk of unnecessary surgical resection for patients who develop early metastatic disease, improved surgical outcomes and the potential for longer overall survival. However, there are no prospective, randomized studies of the neoadjuvant approach compared to a surgeryfirst strategy; the established and ongoing investigations of neoadjuvant therapy for pancreatic cancer are discussed in detail. Lastly, as the future of therapeutic regimens is likely to entail patient-specific genetic and molecular analyses, and the treatment that is best applied based on those data, a review of clinically relevant biomarkers in pancreatic cancer is also presented.

Long-term results of paclitaxel plus cisplatin with concurrent radiotherapy for loco-regional esophageal squamous cell carcinoma

AIM To evaluate the long-term effectiveness and late toxicities of paclitaxel(PTX) plus cisplatin(DDP) with concurrent radiotherapy for locally advanced esophageal squamous cancer.METHODS Between 2008 and 2011, 76 patients were enrolled in a phase Ⅱ study on the treatment of loco-regionally advanced esophageal cancer with radiotherapy(68.4 Gy/44 fractions or 61.2 Gy/34 fractions) combined with 4-cycle chemotherapy consisting of DDP(25 mg/m^2 per day for 3 d) and PTX(175 mg/m^2 for 3 h). The primary endpoints were overall survival and progression-free survival, and the secondary endpoints were toxicity and the treatment failure pattern.RESULTS A total of 76 patients were enrolled in this study, of whom 63.2% finished the whole regimen. The 5-year survival rates for the per-protocol population and intent-to-treat population were 25.4% and 26.4%, respectively, and the median survival rates were 23.7 mo and 28.5 mo, respectively. Grade 3 or 4 late toxicity was observed in only one patient(heart failure). In log-rank analysis, the pretreatment stage(stage Ⅱ + Ⅲ: 36.1 mo vs stage Ⅳ: 14.9 mo) and the completed cycle(1-3 cycles: 16.1 mo vs 4 cycles: 35.5 mo) were significant prognostic factors(P = 0.037 < 0.05 and P = 0.013 < 0.05).CONCLUSION Radiotherapy combined with chemotherapy consisting of PTX and DDP is a safe and effective definitive treatment for loco-regionally advanced esophageal squamous cancer.

A clinical and long-term follow-up study of perioperative sequential triple therapy for gastric cancer

INTRODUCTIONAlthough the long-term postoperative survival rateof gastric cancer(GC) patients has been improvedsignificantly since the local dissection of lymph nodewas widely used in China,yet the low curativeresection rate and the high recurrence rate fromperitoneal and hepatic metastases hinder it fromfurther improvement.To alter the currentunsatisfactory status of GC treatment,a

When combination therapy isn't working: Emerging therapies for the management of inflammatory bowel disease

Although antagonists of tumor necrosis factor have resulted in major therapeutic benefits in inflammatory bowel disease, the magnitude and durability of response are variable. Similar to previously available drugs such as 5-aminosalicylates and immunomodulators, the therapeutic effect is not universal leaving many people searching for options. The development of newer agents has benefited from advances in the understanding of the pathophysiology of the disease. Uncontrolled activation of the acquired immune system has an important role, and lymphocytes, cytokines, and adhesion molecules are broadly targeted for therapeutic intervention. There is increasing evidence of an important role of the innate immune system and the intestinal epithelium, and the therapeutic paradigm is also shifting from immunosuppression to the reinforcement of the intestinal barrier, and modification of the disease process. In this review, we explore the limitation of current therapy as well as mechanisms of actions of new drugs and the efficacy and adverse events from data from clinical trials.

Does ‘super-responder’ patients to cardiac resynchronization therapy still have indications for neuro-hormonal antagonists? Evidence from long-term follow-up in a single center

Background Whether cardiac resynchronization therapy super-responders (CRT-SRs) still have indications for neuro-hormonal antagonists or not remains uninvestigated.Methods We reviewed clinical data from 376 patients who underwent CRT implantation in Fuwai Hospital from 2009 to 2015 and followed up to 2017.CRT-SRs were defined by an improvement of the New York Heart Association functional class and left ventricular ejection fraction to ≥ 50% in absolute values at 6-month follow-up.All CRT-SRs were assigned into two groups on the basis of whether persistently receiving neuro-hormonal antagonists (NHA)(defined as angiotensin-converting enzyme inhibitors/ angiotensin receptor blockers and β-blockers) after 6-month follow-up and then we compared long-term outcome.Results A total of 60 patients met criteria for super-response.One of thirteen (7.7%) CRT-SRs without NHA had all-cause death,which also occurred in 2 of 47 (4.3%) in CRT-SRs with NHA (P = 0.526).However,3 of 13 (23.1%) CRT-SRs without NHA had heart failure (HF) hospitalization,1 of 47 (2.1%) CRT-SRs with NHA had this endpoint (P = 0.040).Besides,subgroup analysis indicated that,for ischemic etiology group,CRT-SRs receiving NHA had considerably lower incidence of HF hospitalization than those without NHA (0 vs.75%,P = 0.014),which was not observed in non-ischemic etiology group (2.6% vs.0,P = 1.000) during long-term follow-up.Conclusions Our study found that for ischemic etiology,compared with CRT-SRs with NHA,CRT-SRs without NHA were associated with a higher risk of HF hospitalization.However,for non-ischemic etiology,we found that CRT-SRs with NHA or without NHA at follow-up were associated with similar outcomes,which needed further investigation by prospective trials.

Long-term follow-up of cumulative incidence of hepatocellular carcinoma in hepatitis B virus patients without antiviral therapy

BACKGROUND China has a high prevalence of hepatitis B virus(HBV),but most chronic hepatitis B(CHB)patients do not receive standardized antiviral therapy.There are few relevant reports addressing the outcomes of the large number of CHB patients who do not receive antiviral therapy.AIM To observe the outcomes of long-term follow-up of patients with CHB without antiviral treatment.METHODS This study included 362 patients with CHB and 96 with hepatitis B cirrhosis without antiviral treatment and with only liver protection and anti-inflammatory treatment from 1993 to 1998.The median follow-up times were 10 and 7 years,respectively.A total of 203 CHB and 129 hepatitis B cirrhosis patients receiving antiviral therapy were selected as the control groups.The median follow-up times were 8 and 7 years,respectively.Kaplan-Meier curves were used to analyze the cumulative incidence of hepatocellular carcinoma(HCC),and the Cox regression model was used to analyze the risk factors for HCC.RESULTS Among the patients in the non-antiviral group,16.9%had spontaneous decreases(HBeAg)seroconversion.In the antiviral group,87.2%of patients had undetectable HBV DNA,and 52%showed HBeAg seroconversion.Among CHB and hepatitis B cirrhosis patients,the cumulative incidence rates of HCC were 14.9%and 53.1%,respectively,in the non-antiviral group and were 10.7%and 31.9%,respectively,in the antiviral group.There was no difference between the two groups regarding the CHB patients(P=0.842),but there was a difference between the groups regarding the hepatitis B cirrhosis patients(P=0.026).The cumulative incidence rates of HCC were 1.6%and 22.3%(P=0.022)in the groups with and without spontaneous HBeAg seroconversion,respectively.The incidence rates of HCC among patients with and without spontaneous declines in HBV DNA to undetectable levels were 1.6%and 19.1%,respectively(P=0.051).There was no difference in the cumulative incidence of HCC between the two groups regarding the patients with drug-resistant CHB(P=0.119),but there was a significant difference between the two groups regarding the patients with cirrhosis(P=0.004).The Cox regression model was used for regression of the corrected REACH-B score,which showed that alanine aminotransferase>400 U/L,history of diabetes,and family history of liver cancer were risk factors for HCC among men aged>40 years(P<0.05).Multifactorial analysis showed that a family history of HCC among men was a risk factor for HCC.CONCLUSION Antiviral therapy and non-antiviral therapy with liver protection and antiinflammatory therapy can reduce the risk of HCC.Antiviral therapy may mask the spontaneous serological response of some patients during CHB.Therefore,the effect of early antiviral therapy on reducing the incidence of HCC cannot be overestimated.

Clinicopathological predictors of long-term benefit in breast cancer treated with neoadjuvant chemotherapy

AIM To investigate the survival impact of clinicopathological factors, including pathological complete response(p CR) and tumor-infiltrating lymphocytes(s TIL) levels according to subtypes, in breast cancer(BC) patients who received neo-adjuvant chemotherapy(NAC).METHODS We evaluated 435 BC patients who presented and received NAC at the Instituto Nacional de Enfermedades Neoplasicas from 2003 to 2014. s TIL was analyzed as the proportion of tumor stroma occupied by lymphocytes, and was prospectively evaluated on hematoxylin and eosin-stained sections of the preN AC core biopsy. p CR was considered in the absence of infiltrating cancer cells in primary tumor and axillary lymph nodes. Analysis of statistical association between clinical pathological features, s TIL, p CR and survival were carried out using SPSSvs19.RESULTS Median age was 49 years(range 24-84 years) and the most frequent clinical stage was ⅢB(58.3%). Luminal A, Luminal B, HER2-enriched and(triple-negative) TN phenotype was found in 24.6%, 37.9%, 17.7% and 19.8%, respectively. p CR was observed in 11% and median percentage of s TIL was 40%(2%-95%) in the whole population. p CR was associated to Ct1-2(P = 0.045) and to high s TIL(P = 0.029) in the whole population. There was a slight trend towards significance for s TIL(P = 0.054) in Luminal A. s TIL was associated with grade Ⅲ(P < 0.001), no-Luminal A subtype(P < 0.001), RE-negative(P < 0.001), PgR-negative(P < 0.001), HER2-positive(P = 0.002) and p CR(P = 0.029) in the whole population. Longer disease-free survival was associated with grade Ⅰ-Ⅱ(P = 0.006), cN 0(P < 0.001), clinical stage Ⅱ(P = 0.004), ER-positive(P < 0.001), Pg R-positive(P < 0.001), luminal A(P < 0.001) and p CR(P = 0.002). Longer disease-free survival was associated with grade Ⅰ-Ⅱ in Luminal A(P < 0.001), N0-1 in Luminal A(P = 0.045) and TNBC(P = 0.01), clinical stage Ⅱ in Luminal A(P = 0.003) and TNBC(P = 0.038), and pC R in TNBC(P < 0.001). Longer overall survival was associated with grade Ⅰ-Ⅱ(P < 0.001), ER-positive(P < 0.001), PgR-positive(P < 0.001), Luminal A(P < 0.001), cN 0(P = 0.002) and p CR(P = 0.002) in the whole population. Overall survival was associated with clinical stage Ⅱ(P = 0.017) in Luminal A, older age(P = 0.042) in Luminal B, and pC R in TNBC(P = 0.005).CONCLUSION Predictive and prognostic values of clinicopathological features, like p CR and s TIL, differ depending on the evaluated molecular subtype.

A study on sleep architecture in patients with chronic respiratory failure under long-term oxygen therapy—Focused on the influence of ventilatory failure (high CO₂) elements on the patient’s sleep architecture

Sleep disturbance related symptoms are common in patients with long-term oxygen therapy (LTOT). Essentially, there were only few previous reports about the sleep architecture in patients with respiratory disease, such as chronic obstructive pulmonary disease (COPD). This study aims to clarify the objective sleep state and the elements that affect sleep architecture in Chronic Respiratory Failure (CRF) patients with focus on clinical cases of chronic hypercapnia. 13 subjects with chronic respiratory failure were enrolled in the study. All the subjects were pre-evaluated by pulmonary function test and Arterial blood gas analysis (ABG) including exercise testing. Polysomnography (PSG) test was performed in each subject with supplemental oxygen. The estimated base line PaCO2 value that reflects overall PaCO2 including sleep period was calculated using equation of PaCO2[2.4×(HCOˉ3)-22]from obtained ABG value just before PSG test. 6 subjects were classified as hypercapnic group (base line PaCO2 ≥ 45 mmHg) and 7 subjects were non-hypercapnic group (base line PaCO2 < 45 mmHg). Latency persistent sleep of PSG data was significant higher in patients with hypercapnic than non-hypercapnic (p < 0.01). Periodic Limb Movement was seen in 23.6% of the subjects, however there was no contribution for arousals. Other PSG data include mean SpO2 were no significant difference. This study suggests that patients with estimated hypercapnia had more disturbed sleep architecture especially significant loss of sleep latency than non-hypercapnic patient with chronic respiratory failure under LTOT. Nocturnal PaCO2 level or ventilatory function may contribute to sleep disturbance in patients with estimated hypercapnia during LTOT.

Low-velocity simultaneous bilateral femoral neck fracture following long-term antiepileptic therapy:A case report

BACKGROUND Simultaneous bilateral femoral neck fractures are relatively rare injuries.They are usually associated with underlying metabolic bone disorders or systemic diseases.Long-term use of narcotics and bisphosphonates can also result in similar fracture patterns;however,association of this fracture type with longterm use of antiepileptic drugs is not very common.Only one such case has been reported in the literature.This article describes the second.CASE REPORT We report a case of simultaneous displaced bilateral femoral neck fractures in a 50-year-old epileptic patient,who had taken phenytoin for the past 3 years.The fractures were a result of low-velocity injury following a fall from the bed.The fractures were managed with a bilateral hemi-replacement arthroplasty.Oral bisphosphonates were given to improve the bone quality in the post-operative period.The patient had a good post-operative outcome,that was sustained throughout the entire follow-up period of 1 year.CONCLUSION Antiepileptic drugs should be supplemented with bisphosphonates and vitamin D to improve bone quality and prevent fractures in epileptic patients.

Loco-regional therapies for patients with hepatocellular carcinoma awaiting liver transplantation: Selecting an optimal therapy

Hepatocellular carcinoma(HCC) is a common, increasingly prevalent malignancy. For all but the smallest lesions, surgical removal of cancer via resection or liver transplantation(LT) is considered the most feasible pathway to cure. Resection- even with favorable survival- is associated with a fairly high rate of recurrence, perhaps since most HCCs occur in the setting of cirrhosis. LT offers the advantage of removing not only the cancer but the diseased liver from which the cancer has arisen, and LT outperforms resection for survival with selected patients. Since time waiting for LT is time during which HCC can progress, locoregional therapy(LRT) is widely employed by transplant centers. The purpose of LRT is either to bridge patients to LT by preventing progression and waitlist dropout, or to downstage patients who slightly exceed standard eligibility criteria initially but can fall within it after treatment. Transarterial chemoembolization and radiofrequency ablation have been the most widely utilized LRTs to date, with favorable efficacy and safety as a bridge to LT(and for the former, as a downstaging modality). The list of potentially effective LRTs has expanded in recent years, and includes transarterial chemoembolization with drug-eluting beads, radioembolization and novel forms of extracorporal therapy. Herein we appraise the various LRT modalities for HCC, and their potential roles in specific clinical scenarios in patients awaiting LT.

Long-Term Chinese Herbs Decoction Administration for Management of Hot Flashes Associated with Endocrine Therapy in Breast Cancer Patients

Objective：To evaluate the effect of Chinese herbs decoction Shu-Gan-Liang-Xue on endocrine therapy-associated hot flashes symptom in breast cancer patients.Methods：Sixty-six patients with breast cancer receiving adjuvant endocrine therapy were categorized to two groups,the control group received endocrine therapy alone,the other group is administered with Chinese herbs decoction Shu-Gan-Liang-Xue besides the endocrine therapy：Shu-Gan-Liang-Xue decoction was administered above 6 months per year for more than 2 years.Frequency of hot flashes per day was recorded,and the effect of Shu-Gan-Liang-Xue decoction on hot flashes symptom being assessed with Kupperman Scoring Index.Results：Sixty cases were analyzed,32 cases in endocrine therapy combining Chinese herbs decoction group,28 cases in mere endocrine therapy group.For hot flashes symptom,in Chinese herbs decoction administration group,7 cases（21.9%） reported symptom disappeared,22 cases（68.7%） reported symptom alleviated,3 cases（9.4%） reported symptom not changed;in endocrine therapy alone group,5 cases（17.9%） reported symptom disappeared,13 cases（46.4%） reported symptom alleviated,10 cases（10/28,35.7%） reported symptom not changed.The difference between two groups was statistically significant（P=0.013）.For sleeping disorder,in Chinese herbs decoction administration group,27 cases（84.4%） reported symptom improved,5 cases（15.6%） reported no change;in endocrine therapy alone group,16 cases（57.1%） symptom improved,12 cases（42.9%） reported no change in sleeping disorder（P=0.019）,the difference was also of significance statistically.Conclusion：Long-term Chinese herbs decoction administration remarkably improved hot flashes symptom and sleeping disorder associated with endocrine therapy,meanwhile without definite toxicity and influence on the risk of recurrence of tumor.

Acute upper gastrointestinal bleeding in patients on long-term oral anticoagulation therapy: Endoscopic findings, clinical management and outcome

AIM: Acute gastrointestinal bleeding is a severe complication in patients receiving long-term oral anticoagulant therapy. The purpose of this study was to describe the causes and clinical outcome of these patients. METHODS: From January 1999 to October 2003, 111 patients with acute upper gastrointestinal bleeding (AUGIB) were hospitalized while on oral anticoagulants. The causes and clinical outcome of these patients were compared with those of 604 patients hospitalized during 2000-2001 with AUGIB who were not taking warfarin. RESULTS: The most common cause of bleeding was peptic ulcer in 51 patients (45%) receiving anticoagulants compared to 359/604 (59.4%) patients not receiving warfarin (P<0.05). No identifiable source of bleeding could be found in 33 patients (29.7%) compared to 31/604 (5.1%) patients not receiving anticoagulants (P=0.0001). The majority of patients with concurrent use of non-steroidal anti-inflammatory drugs (NSAIDs) (26/35, 74.3%) had a peptic ulcer as a cause of bleeding while 32/76 (40.8%) patients not taking a great dose of NSAIDs had a negative upper and lower gastrointestinal endoscopy. Endoscopic hemostasis was applied and no complication was reported. Six patients (5.4%) were operated due to continuing or recurrent hemorrhage, compared to 23/604 (3.8%) patients not receiving anticoagulants. Four patients died, the overall mortality was 3.6% in patients with AUGIB due to anticoagulants, which was not different from that in patients not receiving anticoagulant therapy. CONCLUSION: Patients with AUGIB while on long-term anticoagulant therapy had a clinical outcome, which is not different from that of patients not taking anticoagulants. Early endoscopy is important for the management of these patients and endoscopic hemostasis can be safely applied.