BACKGROUND Bone is the most common site of metastasis in breast cancer,yet limited data exist regarding the precise anatomical distribution of bone metastases by tumor subtype.AIM To examine the anatomical distributio...BACKGROUND Bone is the most common site of metastasis in breast cancer,yet limited data exist regarding the precise anatomical distribution of bone metastases by tumor subtype.AIM To examine the anatomical distribution of the first bone metastases in stage IV breast cancer,stratified by histological subtype.Secondary objectives include analyzing the anatomical distribution of subsequent bone metastases,Metastasis-Free Survival(MFI),Progression-Free Interval(PFI),and overall survival(OS).METHODS A retrospective cohort study was conducted on 107 adult females with stage IV breast cancer and bone metastases between 2013 and 2023.Patients were classified by histological subtype(Luminal A/B,HER2-enriched,and Triple-Negative).First and subsequent bone metastasis locations were identified via computed tomography,positron emission tomography/CT,or magnetic resonance imaging.Survival analyses included MFI,PFI,and OS.RESULTS Rib metastases were significantly more common in HER2-enriched tumors(80%,P=0.041),while scapula/clavicle metastases were more prevalent in Triple-Negative cases(37.5%,P=0.003).Subsequent bone metastases mirrored initial patterns,with pelvic involvement notably higher in HER2-enriched(60%)and luminal B(58%)patients(P=0.046).No significant differences were found in MFI,PFI,or OS among subtypes.Receptor-based analysis showed no significant variation in bone metastasis locations.CONCLUSION Breast cancer subtypes are associated with suggestive bone metastasis patterns—specifically,rib involvement in HER2-enriched and scapula/clavicle in Triple-Negative cases.While anatomical variations exist,they did not translate into differential survival or fracture risk in this cohort.展开更多
Probiotic agents are live microbes or components of microbes that have a positive effect on the host. They exert their action through interplay with the immune system of the host. Some of this effect is local and some...Probiotic agents are live microbes or components of microbes that have a positive effect on the host. They exert their action through interplay with the immune system of the host. Some of this effect is local and some is systemic. The full story is yet to be discovered. Probiotics have a definite positive effect on rotavirus diarrhea, post antibiotic diarrhea and pouchitis. Their exact role in inflammatory bowel disease, irritable bowel syndrome, other forms of infectious diarrhea, and prevention of cancer is yet to be determined. This review summarizes the data about probiotics in these conditions.展开更多
AIM:To review and summerize the current literatue regarding M2A wireless capsule endoscopy. METHODS:Peer reviewed publications regarding the use of capsule endoscopy as well as our personal experience were reviewed. R...AIM:To review and summerize the current literatue regarding M2A wireless capsule endoscopy. METHODS:Peer reviewed publications regarding the use of capsule endoscopy as well as our personal experience were reviewed. RESULTS:Review of the literature dearly showed that capsule endoscopy was superior to enteroscopy,small bowel follow through and computerized tomography in patients with obscure gastrointestinal bleeding,iron deficiency anemia, or suspected Crohn's disease.It was very sensitive for the diagnosis of small bowel tumors and for survailance of small bowel pathology in patients with Gardner syndrome or familial adenomatous polyposis syndrome.Its role in celiac disease and in patients with known Crohn's disease was currently being investigated. CONCLUSION:Capsule video endoscopy is a superior and more sensitive diagnostic tool than barium follow through, enteroscopy and entero-CT in establishing the diagnosis of many small bowel pathologies.展开更多
AIM：To compare accuracy,reproducibility and test duration for the Snellen and the Early Treatment Diabetic Retinopathy Study（ETDRS）charts,two main tools used to measure visual acuity（VA）.·M ETHODS：A compute...AIM：To compare accuracy,reproducibility and test duration for the Snellen and the Early Treatment Diabetic Retinopathy Study（ETDRS）charts,two main tools used to measure visual acuity（VA）.·M ETHODS：A computer simulation was programmed to run multiple virtual patients,each with a unique set of assigned parameters,including VA,false-positive and false-negative error values.For each virtual patient,assigned VA was randomly chosen along a continuous scale spanning the range between 1.0 to 0.0 log MAR units（equivalent to 20/200 to 20/20）.Each of 30 000virtual patients were run ten times on each of the two VA charts.·RESULTS：Average test duration（expressed as the total number of characters presented during the test±SD）was12.6±11.1 and 31.2±14.7 characters,for the Snellen and ETDRS,respectively.Accuracy,defined as the absolute difference（±SD）between the assigned VA and the measured VA,expressed in log MAR units,was superior in the ETDRS charts：0.12±0.14 and 0.08±0.08,for the Snellen and ETDRS charts,respectively.Reproducibility,expressed as test-retest variability,was superior in the ETDRS charts：0.23±0.17 and 0.11±0.09 log MAR units,for the Snellen and ETDRS charts,respectively.·CONCLUSION：A comparison of true（assigned）VA to measured VA,demonstrated,on average,better accuracy and reproducibility of the ETDRS chart,but at the penalty of significantly longer test duration.These differences were most pronounced in the low VA range.The reproducibility using a simulation approach is in line with reproducibility values found in several clinical studies.展开更多
AIM：To compare changes in visual acuity and macular edema in patients with central retinal vein occlusion（CRVO）treated with intravitreal injections of bevacizumab,macular grid photocoagulation combined with pan ret...AIM：To compare changes in visual acuity and macular edema in patients with central retinal vein occlusion（CRVO）treated with intravitreal injections of bevacizumab,macular grid photocoagulation combined with pan retinal photocoagulation（PRP）,or both（bevacizumab＋grid＋PRP）.· METHODS：Our study is a retrospective cohort clinical study that examined patients that suffered from ischemic CRVO with macular edema.Study inclusion criteria were ischemic CRVO with macula edema and the availability of complete medical records for at least 12 mo after treatment.Excluded were patients with diabetes or any other retinal disease.We reviewed the medical records of patients treated in one ophthalmology departmentcomparing changes in visual acuity and macular edema in patients treated with intravitreal injections of bevacizumab vs those that were treated with macular grid photocoagulation and PRP or both.The main outcome measures were the differences in best corrected visual acuity（BCVA） and in macular thickness,as assessed by optical coherence tomography,between the enrollment and the final follow up visits.· RESULTS：Sixty-five patients met inclusion criteria.There were no statistically significant differences among the three groups in the mean changes in macular thickness as measured by ocular coherence tomography（131.5±41.2,108.6±29.2,and 121.1±121.1,P=0.110）,or in visual acuity（0.128±0.077,0.088±0.057,and 0.095±0.065）,for intravitreal injections,macular grid photocoagulation＋PRP and a combination of the treatments,respectively,P =0.111.The proportions of patients with macular edema after treatment were：26.1%,28.6%,and 14.3%,respectively,P=0.499.· CONCLUSION：Similar benefit was observed for intravitreal injections,laser photocoagulation,or a combined regimen in the treatment of CRVO.A nonstatistically significant trend for reduction in macular edema was observed following combined treatment.展开更多
AIM:To study the management and outcome of children with extrahepatic portal vein obstruction(EHPVO) in a whole country population.METHODS:A nationwide multicenter retrospective case series of children with EHPVO was ...AIM:To study the management and outcome of children with extrahepatic portal vein obstruction(EHPVO) in a whole country population.METHODS:A nationwide multicenter retrospective case series of children with EHPVO was conducted.Data on demographics,radiographic studies,laboratory workup,endoscopic and surgical procedures,growth and development,were extracted from the patients' charts.Characteristics of clinical presentation,etiology of EHPVO,management and outcome were analyzed.RESULTS:Thirty patients,13 males and 17 females,19(63.3%) Israeli and 11(36.7%) Palestinians,were included in the analysis.Age at presentation was 4.8± 4.6 years,and mean follow-up was 4.9±4.3 years.Associated anomalies were found in 4 patients.The incidence of EHPVO in Israeli children aged 0-14 years was 0.72/million.Risk factors for EHPVO were detected in 13(43.3%)patients,including 9 patients(30%) with perinatal risk factors,and 4 patients(13.3%) with prothrombotic states:two had low levels of protein S and C,one had lupus anticoagulant,and one was homozygous for methyltetrahydrofolate reductase mutations.In 56.6% of patients,no predisposing factors were found.The most common presenting symptoms were an incidental finding of splenomegaly(43.3%),and upper gastrointestinal bleeding(40%).No differences were found between Israeli and Palestinian children with regard to age at presentation,etiology and clinical symptoms.Bleeding occurred in 18 patients(60%),at a median age of 3 years.Sclerotherapy or esophageal banding was performed in 20 patients.No sclerotherapy complications were reported.Portosystemic shunts were performed in 11 patients(36.6%),at a median age of 11(range 3-17)years:splenorenal in 9,mesocaval in 1,and a meso-Rex shunt in 1 patient.One patient underwent splenectomy due to severe pancytopenia.Patients were followed up for a median of 3(range 0.5-15)years.One patient died aged 3 years due to mucopolysaccharidase deficiency type Ⅲ.None of the patients died due to gastrointestinal bleeding.CONCLUSION:EHPVO is a rare disorder.The etiological factors are still mostly unknown,and the endoscopic and surgical treatment options ensure a good long-term prognosis.展开更多
Schizophrenia is a severe mental disorder, characterized by behavioral, emotional and cognitive disturbances,which commonly follows a chronic course. Diagnostic accuracy, management plans, treatment evaluation and pro...Schizophrenia is a severe mental disorder, characterized by behavioral, emotional and cognitive disturbances,which commonly follows a chronic course. Diagnostic accuracy, management plans, treatment evaluation and prognosis are dependent on relatively subjective assessments. Despite extensive research and improvement in imaging technology, as well as modern genetic and molecular methodologies, the biological basis of this disease is still unclear. Therefore, there is a need for objective and valid biological markers. Platelets have often been used as a model in neurobiological research. The accessibility of platelets and their similarities with neurons turns them into an attractive candidate to search for biological markers for diagnosis and for unraveling pathophysiological processes relevant to the etiology of brain disorders, including schizophrenia.The present review addresses the main changes in platelet physiology observed in schizophrenia and its response to antipsychotic medication. We summarize numerous studies demonstrating impaired metabolism,uptake and receptor kinetics of schizophrenia-relevantneurotransmitters, abnormalities in membrane derived phospholipids and polyunsaturated fatty acids, as well as dysfunctions in the mitochondria. These changes fit with the various hypotheses raised for the etiology of schizophrenia, including the dopamine-glutamate hypothesis, the autoimmune hypothesis, the polyunsaturated fatty acid hypothesis and the impaired energy metabolism hypothesis. Despite extensive research in platelets, no conclusive reliable biomarker has been identified yet. This review suggests that the clinical heterogeneity and the biological complexity of schizophrenia lead to the inevitable conclusion that biomarkers will be identified only for subgroups characterized according to the different diagnostic criteria. Moreover, any biomarker would have to be an array of interrelated factors or even a set of several such arrays.展开更多
It is generally assumed that behavior results from an interaction between susceptible genes and environmental stimuli during critical life stages.The present article reviews the main theoretical and practical concepts...It is generally assumed that behavior results from an interaction between susceptible genes and environmental stimuli during critical life stages.The present article reviews the main theoretical and practical concepts in the research of gene environment interaction,emphasizing the need for models simulating real life complexity.We review a novel approach to study gene environment interaction in which a brief post-natal interference with the expression of multiple genes,by hindering the activity of the ubiquitous transcription factor specificity protein 1(Sp1) is followed by later-in-life exposure of rats to stress.Finally,this review discusses the role of peripheral processes in behavioral responses,with the Sp1 model as one example demonstrating how specific behavioral patterns are linked to modulations in both peripheral and central physiological processes.We suggest that models,which take into account the tripartite reciprocal interaction between the central nervous system,peripheral systems and environmental stimuli will advance our understanding of the complexity of behavior.展开更多
BACKGROUND： Caffeinated energy drinks are with a variety of adverse effects and are of concern information about their adverse effects and inadequate widely used worldwide. They are associated to health authorities, ...BACKGROUND： Caffeinated energy drinks are with a variety of adverse effects and are of concern information about their adverse effects and inadequate widely used worldwide. They are associated to health authorities, yet there is still scarce awareness among medical personnel.METHODS： Case description and discussion of a patient presenting to the emergency room after overdose of energy drinks in combination with 3,4-methylenedioxymethamphetamine （MDMA）.RESULTS： Despite best medical efforts, the patient died of fatal cardiac arrhythmias. There is a paucity of information about adverse effects of energy drinks.CONCLUSION： Although energy drinks are widely used, there is a lack of awareness in the population and medical staff about their hazards.展开更多
OBJECTIVES: This study was designed to assess the feasibility and safety of a Remote Navigation System(RNS, NaviCath, Haifa, Israel) in which the angioplasty guidewire, the balloon, and the stent are navigated via a c...OBJECTIVES: This study was designed to assess the feasibility and safety of a Remote Navigation System(RNS, NaviCath, Haifa, Israel) in which the angioplasty guidewire, the balloon, and the stent are navigated via a computerized system. BACKGROUND: Percutaneous coronary interventions(PCIs) are manually performed under fluoroscopic guidance, requiring lead protection for the operators. A system in which the operator can remotely, safely, and precisely navigate the procedure during PCI would have clear advantages. METHODS: The RNS involves a computer-controlled wire and delivery system navigator. Following preclinical validation, the system was assessed in patients undergoing single-vessel PCI. RESULTS: The study involved 18 patients(age 55.9 years, 16% women). The RNS successfully crossed lesions with the guidewire in 17 patients. The stent was then advanced by the advance/rotate mode and adequately positioned in 15 of 17 cases. Technical malfunction was encountered in three patients in whom the procedure was successfully completed manually. Direct stenting was employed in 10 of 18 patients,pre-dilation in 7 patients, and after-stent balloon dilation in 5 patients. The total fluoroscopy time for 17 RNS patients was compared with the corresponding time of 20 consecutive patients who underwent standard single lesion PCI. Fluoroscopy time was similar for both procedures, with 8.8± 4.8 min with the RNS versus 9.1± 3.5 min with the standard techniques(p=NS). Clinical success was 100% and technical success 94% for the guidewire and 83% for the overall procedure. CONCLUSIONS: The use of the RNS for guidewire, balloon, and stent manipulation during PCI appears safe and feasible for the treatment of patients with coronary stenosis. The system offers operator radiation safety and may enhance precision of stent placement and balloon dilation strategies.展开更多
BACKGROUND:Dyspnea is one of the most common complaints facing the emergency medicine physician.Some of the gastrointestinal causes of dyspnea are self-limited and not lifethreatening,yet others are,and early diagnosi...BACKGROUND:Dyspnea is one of the most common complaints facing the emergency medicine physician.Some of the gastrointestinal causes of dyspnea are self-limited and not lifethreatening,yet others are,and early diagnosis and treatment are crucial.METHODS:In this article we presented one of these life-threatening conditions through a clinical description of a patient presenting with acute respiratory distress that was finally diagnosed to be the result of a perforated gastric ulcer.RESULTS:An emergent thoracotomy revealed a small ulcer with perforation in the fundus of the stomach.The patient was transferred after the operation to the intensive care unit and after a prolonged hospitalization discharged home.Biopsies taken from the ulcer showed diffuse inflammation,with no evidence of microorganisms or malignancy.CONCLUSION:Perforation of gastric and duodenal ulcers is a rare yet existing cause of dyspnea and respiratory failure and should be kept in mind by the emergency physician,especially when other more common causes are ruled out.展开更多
Objective: To evaluate the effect of inhaled dexamethasone on hospitalization for respiratory syncytial virus (RSV) bronchiolitis. Study design: A double-bli nd, placebo-controlled study compared nebulization of dexam...Objective: To evaluate the effect of inhaled dexamethasone on hospitalization for respiratory syncytial virus (RSV) bronchiolitis. Study design: A double-bli nd, placebo-controlled study compared nebulization of dexamethasone versus nebu lization of 0.9%saline. Both groups were treated with epinephrine nebulizations . Follow-up continued for 3 mo. Patients and methods: Sixty-one infants with b ronchiolitis aged 3 to 12 mo were included. They were randomly allocated to nebu lizations with 0.25 mg dexamethasone every 6 h (group 1) or an equivalent amount of normal saline (group 2). Results: No statistically significant differences w ith respect to clinical score, oxygen saturation, or IV fluid requirement betwee n the groups were noted. Using Kaplan-Meyer’s method, the cumulative proportio n of in-hospital stay was significantly lower in group 1 compared with group 2, mainly in days 5 and 6 post-hospitalization (p < 0.038). A subgroup of prematu rely born children in group 1 had a shorter hospitalization period (6.5 ±1.7 d) compared with group 2 children (9.1 ±1.9) (p < 0.018). Follow-up revealed sim ilar wheeze and hospitalization rates in the two groups. Conclusion: Inhaled dex amethasone may reduce the length of hospitalization among infants with acute vir al bronchiolitis, especially among those born prematurely.展开更多
Women with thrombophilia and a history of recurrent pregnancy loss have poor pregnancy outcomes. Prophylaxis with enoxaparin 40 mg/day or 80 mg/day resulted in favorable gestational and neonatal outcomes.
AIM: To evaluate daclatasvir vs telaprevir, each combined with peginterferon alfa-2a/ribavirin(peg IFN/RBV), in treatment-naive hepatitis C virus(HCV) genotype(GT) 1-infected patients.METHODS: In this phase 3, randomi...AIM: To evaluate daclatasvir vs telaprevir, each combined with peginterferon alfa-2a/ribavirin(peg IFN/RBV), in treatment-naive hepatitis C virus(HCV) genotype(GT) 1-infected patients.METHODS: In this phase 3, randomized, open-label, noninferiority study, 602 patients were randomly assigned(2:1) to daclatasvir vs telaprevir, stratified by IL28 B rs12979860 host genotype(CC vs non-CC), cirrhosis status(compensated cirrhosis vs no cirrhosis), and HCV GT1 subtype(GT1a vs GT1b). Patients were selected by study inclusion criteria from a total of 793 enrolled patients. Patients received daclatasvir 60 mg once daily or telaprevir 750 mg 3 times daily plus peg IFN/RBV. Daclatasvir recipients received 24 wk of daclatasvir plus peg IFN/RBV; those without an extended rapid virologic response(e RVR; undetectable HCV-RNA at weeks 4 and 12) received an additional 24 wk of peg IFN/RBV. Telaprevir-treated patients received 12 wk of telaprevir plus peg IFN/RBV followed by 12(with e RVR) or 36(no e RVR) wk of peg IFN/RBV. The primary objective was to compare for noninferiority of sustained virologic response rates at posttreatment week 12(SVR12) in GT1b-infected patients. Key secondary objectives were to demonstrate that the rates of anemia(hemoglobin < 10 g/d L) and rashrelated events, through week 12, were lower with daclatasvir + peg IFN/RBV than with telaprevir + peg IFN/RBV among GT1b-infected patients. Resistance testing was performed using population-based sequencing of the NS5 A region for all patients at baseline, and for patients with virologic failure or relapse and HCV-RNA ≥ 1000 IU/m L, to investigate any link between NS5 A polymorphisms associated with daclatasvir resistance and virologic outcome. RESULTS: Patient demographics and disease characteristics were generally balanced across treatment arms; however, there was a higher proportion of black/African Americans in the daclatasvir groups(6.0% and 8.2% in the GT1 b and GT1 a groups, respectively) than in the telaprevir groups(2.2% and 3.0%). Among GT1 binfected patients, daclatasvir plus peg IFN/RBV was noninferior to telaprevir plus peg IFN/RBV for SVR12 [85%(228/268) vs 81%(109/134); difference, 4.3%(95%CI:-3.3% to 11.9%)]. Anemia(hemoglobin < 10 g/d L) was significantly less frequent with daclatasvir than with telaprevir [difference,-29.1%(95%CI:-38.8% to-19.4%)]. Rash-related events were also less common with daclatasvir than with telaprevir, but the difference was not statistically significant. In GT1 ainfected patients, SVR12 was 64.9% with daclatasvir and 69.7% with telaprevir. Among both daclatasvir and telaprevir treatment groups, across GT1b- or GT1a-infected patients, lower response rates were observed in patients with IL28 B non-CC and cirrhosis- factors known to affect response to peg IFN/RBV. Consistent with these observations, a multivariate logistic regression analysis in GT1b-infected patients d e m o n s t ra t e d t h a t S V R 1 2 wa s a s s o c i a t e d w i t h IL28 B host genotype(CC vs non-CC, P = 0.011) and cirrhosis status(absent vs present, P = 0.031). NS5 A polymorphisms associated with daclatasvir resistance(at L28, R30, L31, or Y93) were observed in 17.3% of GT1b-infected patients at baseline; such variants did not appear to be absolute predictors of failure since 72.1% of these patients achieved SVR12 compared with 86.9% without these polymorphisms. Among GT1b-infected patients, treatment was completed by 85.4%(229/268) in the daclatasvir group, and by 85.1%(114/134) in the telaprevir group, and among GT1a-infected patients, by 67.2%(90/134) and 69.7%(46/66), respectively. Discontinuations(of all 3 agents) due to an AE were more frequent with telaprevir than with daclatasvir, whereas discontinuations due to lack of efficacy were more frequent with daclatasvir, due, in part, to differences in futility criteria. CONCLUSION: Daclatasvir plus peg IFN/RBV demonstrated noninferiority to telaprevir plus peg IFN/RBV for SVR12 and was well-tolerated in treatment-naive GT1 binfected patients, supporting the use of daclatasvir with other direct-acting antivirals.展开更多
Ectodermal dysplasia/skin fragility syndrome (EDSFS)- (MIM604536) is a newly described autosomal recessive disorder characterized by skin fragility and blistering, palmoplantar keratoderma, abnormal hair growth, nail ...Ectodermal dysplasia/skin fragility syndrome (EDSFS)- (MIM604536) is a newly described autosomal recessive disorder characterized by skin fragility and blistering, palmoplantar keratoderma, abnormal hair growth, nail dystrophy, and occasionally defective sweating. It results from mutations in the PKP1 gene encoding plakophilin 1 (PKP1), which is an important component of stratifying epithelial desmosomes and a nuclear component of many cell types. Our study was performed to further characterize the histopathology of EDSFS in different cutaneous sites with a special emphasis on the hypotrichosis and keratoderma. A total of 4 biopsies were obtained from 2 EDSFS female patients, aged 9 days to 4 years. The biopsies were taken from the blistering skin of the leg and trunk, the hyperkeratotic skin of the sole, and the hypotrichotic scalp. The observed histopathologic features included: widened intercellular spaces, suprabasal intraepidermal clefts and blisters with acantholytic keratinocytes, detachments of the upper epidermal layers due to disadhesion, varying degrees of dyskeratosis thatweremuchmore pronounced in the plantar hyperkeratotic skin, and increased number of catagen- telogen hair follicles. The electron- microscopic observations attributed the disadhesion and acantholysis to reduced numbers of small hypoplastic desmosomes, and the dyskeratosis to the detachment of intracellular keratin filaments from the desmosomes with perinuclear condensation, which might also underlie the plantar keratoderma. The hair follicle findings suggest disturbance in the hair cycle, which might be attributed to disturbed nuclear PKP1 function or result from aberrant desmosomal signaling.展开更多
Objective: To establish the unique and common clinical and microscopic characteristics of the alopecias associated with vitamin D-dependent rickets (VDDR) type IIA and with hairless gene mutations. Design: A comparati...Objective: To establish the unique and common clinical and microscopic characteristics of the alopecias associated with vitamin D-dependent rickets (VDDR) type IIA and with hairless gene mutations. Design: A comparative clinical, histologic, and immunohistochemical study of the alopecias in 6 patients withVDDRIIA and 4 patientswith atrichia with papular lesions (APL) and/or alopecia universalis congenita (AUC) (hereinafter “ APL/AUC” ). Main Outcome Measures: Clinical data were gathered from medical records, personal interviews, and physical examinations. Histologic and immunohistochemical studies were performed on 6 scalp punch biopsy specimens from each of the 2 studied groups. Results: The alopecias in VDDR IIA and APL/AUC showed similar clinical, histologic, and immunohistochemical features. The clinical presentation of the VDDR alopecia resembled either the APL phenotype (ie, with papules and milia) or the AUC phenotype (without papules and milia). The main histologic findings included void infundibula; absence of the lower two thirds of the hair follicles, often replaced by vertically oriented irregular epithelial structures or epithelial cysts; irregular epithelial structures, often with small cysts in the middle and lower dermis; and small, medium, and large keratinizing cysts at all levels of the dermis. The larger epithelial cysts in the upper dermis stained positively for cytokeratin (CK) 10, which suggests an infundibular derivation, whereas the remaining irregular epithelial structures and cysts in themiddle and lower dermis stained positivelymost frequently forCK17, CK19, andCD34,which suggests an outer root sheath derivation. Conclusions: The alopecias associated with VDDR IIA and with hairless gene mutations show striking clinical and microscopic similarities. Disintegration of the lower two thirds of the hair follicles seems to be the underlying defect, and a common pathogenetic pathwaymight be involved.展开更多
Background. Prolidase deficiency is a complex disease characterized by various skin manifestations accompanied by mental retardation, facial dysmorphism and susceptibility to pyogenic infections. Methods. We assessed ...Background. Prolidase deficiency is a complex disease characterized by various skin manifestations accompanied by mental retardation, facial dysmorphism and susceptibility to pyogenic infections. Methods. We assessed a patient presenting a peculiar phenotype combining manifestations of prolidase deficiency with features typical of hyper-IgE syndrome. Mutation analysis was performed using direct PCR amplification and PCR restriction fragment length polymorphism analysis. Results. We identified a novel homozygous recessive mutation in the PEPD gene, which was found to segregate in the family of the patient with the disease and was not found in a panel of DNA samples representative of all major Druze families living in northern Israel. Discussion. Our results suggest that prolidase deficiency associated with hyper-IgE syndrome, a rare disorder, can be caused by mutations in PEPD.展开更多
Objective： Primary uterine leiomyosarcomas （ULMS） are rare, and the optimal treatment is controversial. We aimed to assess the outcome and prognostic factors in a multicenter population of women treated for primary...Objective： Primary uterine leiomyosarcomas （ULMS） are rare, and the optimal treatment is controversial. We aimed to assess the outcome and prognostic factors in a multicenter population of women treated for primary ULMS. Methods： We retrospectively collected data of 110 women treated in 19 institutions of the Rare Cancer Network （RCN）. Inclusion criteria consisted of a pathology report confirming the diagnosis of ULMS, aged 18-80 years, complete International Federation of Gynecology and Obstetrics （FIGO） stage information, complete information on treatment, and a minimum follow-up of 6 months. Local control （LC） and locoregional control （LRC）, overall survival （OS） and disease-free survival （DFS） rates were computed using the Kaplan-Meier method. Univariate analysis was implemented using the log rank test, and multivariate analysis using the Cox model. Results： All patients underwent surgery. Seventy-five patients （68%） received adjuvant radiotherapy （RT）, including brachytherapy in 18 （I 6%）. Seventeen patients （15 %） received adjuvant chemotherapy. Median follow-up was 58 （range, 6-240） months. Five-year OS and DFS rates were 50% and 34%, and LC and LRC rates were 88% and 72%, respectively. On multivariate analysis, independent favorable prognostic factors were younger age, FIGO stage I, small tumor size, previous uterine disease, and no vascular invasion for OS and DFS. FIGO stage was the only favorable factor influencing LRC. Adjuvant local or systemic treatments did not improve the outcomes. Eight patients treated with RT presented a grade 3 acute toxicity, and only one patient with grade 3 late toxicity. Conclusions： In this large population of primary ULMS patients, we found good results in terms of LC and LRC. Nevertheless, OS remains poor, mainly due to the occurrence of distant metastases. An early diagnosis seemed to improve the prognosis of the patients. Adjuvant local or systemic treatments, or more aggressive surgical procedures such as the Wertheim procedure, did not seem to impact the outcome.展开更多
文摘BACKGROUND Bone is the most common site of metastasis in breast cancer,yet limited data exist regarding the precise anatomical distribution of bone metastases by tumor subtype.AIM To examine the anatomical distribution of the first bone metastases in stage IV breast cancer,stratified by histological subtype.Secondary objectives include analyzing the anatomical distribution of subsequent bone metastases,Metastasis-Free Survival(MFI),Progression-Free Interval(PFI),and overall survival(OS).METHODS A retrospective cohort study was conducted on 107 adult females with stage IV breast cancer and bone metastases between 2013 and 2023.Patients were classified by histological subtype(Luminal A/B,HER2-enriched,and Triple-Negative).First and subsequent bone metastasis locations were identified via computed tomography,positron emission tomography/CT,or magnetic resonance imaging.Survival analyses included MFI,PFI,and OS.RESULTS Rib metastases were significantly more common in HER2-enriched tumors(80%,P=0.041),while scapula/clavicle metastases were more prevalent in Triple-Negative cases(37.5%,P=0.003).Subsequent bone metastases mirrored initial patterns,with pelvic involvement notably higher in HER2-enriched(60%)and luminal B(58%)patients(P=0.046).No significant differences were found in MFI,PFI,or OS among subtypes.Receptor-based analysis showed no significant variation in bone metastasis locations.CONCLUSION Breast cancer subtypes are associated with suggestive bone metastasis patterns—specifically,rib involvement in HER2-enriched and scapula/clavicle in Triple-Negative cases.While anatomical variations exist,they did not translate into differential survival or fracture risk in this cohort.
文摘Probiotic agents are live microbes or components of microbes that have a positive effect on the host. They exert their action through interplay with the immune system of the host. Some of this effect is local and some is systemic. The full story is yet to be discovered. Probiotics have a definite positive effect on rotavirus diarrhea, post antibiotic diarrhea and pouchitis. Their exact role in inflammatory bowel disease, irritable bowel syndrome, other forms of infectious diarrhea, and prevention of cancer is yet to be determined. This review summarizes the data about probiotics in these conditions.
文摘AIM:To review and summerize the current literatue regarding M2A wireless capsule endoscopy. METHODS:Peer reviewed publications regarding the use of capsule endoscopy as well as our personal experience were reviewed. RESULTS:Review of the literature dearly showed that capsule endoscopy was superior to enteroscopy,small bowel follow through and computerized tomography in patients with obscure gastrointestinal bleeding,iron deficiency anemia, or suspected Crohn's disease.It was very sensitive for the diagnosis of small bowel tumors and for survailance of small bowel pathology in patients with Gardner syndrome or familial adenomatous polyposis syndrome.Its role in celiac disease and in patients with known Crohn's disease was currently being investigated. CONCLUSION:Capsule video endoscopy is a superior and more sensitive diagnostic tool than barium follow through, enteroscopy and entero-CT in establishing the diagnosis of many small bowel pathologies.
文摘AIM：To compare accuracy,reproducibility and test duration for the Snellen and the Early Treatment Diabetic Retinopathy Study（ETDRS）charts,two main tools used to measure visual acuity（VA）.·M ETHODS：A computer simulation was programmed to run multiple virtual patients,each with a unique set of assigned parameters,including VA,false-positive and false-negative error values.For each virtual patient,assigned VA was randomly chosen along a continuous scale spanning the range between 1.0 to 0.0 log MAR units（equivalent to 20/200 to 20/20）.Each of 30 000virtual patients were run ten times on each of the two VA charts.·RESULTS：Average test duration（expressed as the total number of characters presented during the test±SD）was12.6±11.1 and 31.2±14.7 characters,for the Snellen and ETDRS,respectively.Accuracy,defined as the absolute difference（±SD）between the assigned VA and the measured VA,expressed in log MAR units,was superior in the ETDRS charts：0.12±0.14 and 0.08±0.08,for the Snellen and ETDRS charts,respectively.Reproducibility,expressed as test-retest variability,was superior in the ETDRS charts：0.23±0.17 and 0.11±0.09 log MAR units,for the Snellen and ETDRS charts,respectively.·CONCLUSION：A comparison of true（assigned）VA to measured VA,demonstrated,on average,better accuracy and reproducibility of the ETDRS chart,but at the penalty of significantly longer test duration.These differences were most pronounced in the low VA range.The reproducibility using a simulation approach is in line with reproducibility values found in several clinical studies.
文摘AIM：To compare changes in visual acuity and macular edema in patients with central retinal vein occlusion（CRVO）treated with intravitreal injections of bevacizumab,macular grid photocoagulation combined with pan retinal photocoagulation（PRP）,or both（bevacizumab＋grid＋PRP）.· METHODS：Our study is a retrospective cohort clinical study that examined patients that suffered from ischemic CRVO with macular edema.Study inclusion criteria were ischemic CRVO with macula edema and the availability of complete medical records for at least 12 mo after treatment.Excluded were patients with diabetes or any other retinal disease.We reviewed the medical records of patients treated in one ophthalmology departmentcomparing changes in visual acuity and macular edema in patients treated with intravitreal injections of bevacizumab vs those that were treated with macular grid photocoagulation and PRP or both.The main outcome measures were the differences in best corrected visual acuity（BCVA） and in macular thickness,as assessed by optical coherence tomography,between the enrollment and the final follow up visits.· RESULTS：Sixty-five patients met inclusion criteria.There were no statistically significant differences among the three groups in the mean changes in macular thickness as measured by ocular coherence tomography（131.5±41.2,108.6±29.2,and 121.1±121.1,P=0.110）,or in visual acuity（0.128±0.077,0.088±0.057,and 0.095±0.065）,for intravitreal injections,macular grid photocoagulation＋PRP and a combination of the treatments,respectively,P =0.111.The proportions of patients with macular edema after treatment were：26.1%,28.6%,and 14.3%,respectively,P=0.499.· CONCLUSION：Similar benefit was observed for intravitreal injections,laser photocoagulation,or a combined regimen in the treatment of CRVO.A nonstatistically significant trend for reduction in macular edema was observed following combined treatment.
文摘AIM:To study the management and outcome of children with extrahepatic portal vein obstruction(EHPVO) in a whole country population.METHODS:A nationwide multicenter retrospective case series of children with EHPVO was conducted.Data on demographics,radiographic studies,laboratory workup,endoscopic and surgical procedures,growth and development,were extracted from the patients' charts.Characteristics of clinical presentation,etiology of EHPVO,management and outcome were analyzed.RESULTS:Thirty patients,13 males and 17 females,19(63.3%) Israeli and 11(36.7%) Palestinians,were included in the analysis.Age at presentation was 4.8± 4.6 years,and mean follow-up was 4.9±4.3 years.Associated anomalies were found in 4 patients.The incidence of EHPVO in Israeli children aged 0-14 years was 0.72/million.Risk factors for EHPVO were detected in 13(43.3%)patients,including 9 patients(30%) with perinatal risk factors,and 4 patients(13.3%) with prothrombotic states:two had low levels of protein S and C,one had lupus anticoagulant,and one was homozygous for methyltetrahydrofolate reductase mutations.In 56.6% of patients,no predisposing factors were found.The most common presenting symptoms were an incidental finding of splenomegaly(43.3%),and upper gastrointestinal bleeding(40%).No differences were found between Israeli and Palestinian children with regard to age at presentation,etiology and clinical symptoms.Bleeding occurred in 18 patients(60%),at a median age of 3 years.Sclerotherapy or esophageal banding was performed in 20 patients.No sclerotherapy complications were reported.Portosystemic shunts were performed in 11 patients(36.6%),at a median age of 11(range 3-17)years:splenorenal in 9,mesocaval in 1,and a meso-Rex shunt in 1 patient.One patient underwent splenectomy due to severe pancytopenia.Patients were followed up for a median of 3(range 0.5-15)years.One patient died aged 3 years due to mucopolysaccharidase deficiency type Ⅲ.None of the patients died due to gastrointestinal bleeding.CONCLUSION:EHPVO is a rare disorder.The etiological factors are still mostly unknown,and the endoscopic and surgical treatment options ensure a good long-term prognosis.
文摘Schizophrenia is a severe mental disorder, characterized by behavioral, emotional and cognitive disturbances,which commonly follows a chronic course. Diagnostic accuracy, management plans, treatment evaluation and prognosis are dependent on relatively subjective assessments. Despite extensive research and improvement in imaging technology, as well as modern genetic and molecular methodologies, the biological basis of this disease is still unclear. Therefore, there is a need for objective and valid biological markers. Platelets have often been used as a model in neurobiological research. The accessibility of platelets and their similarities with neurons turns them into an attractive candidate to search for biological markers for diagnosis and for unraveling pathophysiological processes relevant to the etiology of brain disorders, including schizophrenia.The present review addresses the main changes in platelet physiology observed in schizophrenia and its response to antipsychotic medication. We summarize numerous studies demonstrating impaired metabolism,uptake and receptor kinetics of schizophrenia-relevantneurotransmitters, abnormalities in membrane derived phospholipids and polyunsaturated fatty acids, as well as dysfunctions in the mitochondria. These changes fit with the various hypotheses raised for the etiology of schizophrenia, including the dopamine-glutamate hypothesis, the autoimmune hypothesis, the polyunsaturated fatty acid hypothesis and the impaired energy metabolism hypothesis. Despite extensive research in platelets, no conclusive reliable biomarker has been identified yet. This review suggests that the clinical heterogeneity and the biological complexity of schizophrenia lead to the inevitable conclusion that biomarkers will be identified only for subgroups characterized according to the different diagnostic criteria. Moreover, any biomarker would have to be an array of interrelated factors or even a set of several such arrays.
文摘It is generally assumed that behavior results from an interaction between susceptible genes and environmental stimuli during critical life stages.The present article reviews the main theoretical and practical concepts in the research of gene environment interaction,emphasizing the need for models simulating real life complexity.We review a novel approach to study gene environment interaction in which a brief post-natal interference with the expression of multiple genes,by hindering the activity of the ubiquitous transcription factor specificity protein 1(Sp1) is followed by later-in-life exposure of rats to stress.Finally,this review discusses the role of peripheral processes in behavioral responses,with the Sp1 model as one example demonstrating how specific behavioral patterns are linked to modulations in both peripheral and central physiological processes.We suggest that models,which take into account the tripartite reciprocal interaction between the central nervous system,peripheral systems and environmental stimuli will advance our understanding of the complexity of behavior.
文摘BACKGROUND： Caffeinated energy drinks are with a variety of adverse effects and are of concern information about their adverse effects and inadequate widely used worldwide. They are associated to health authorities, yet there is still scarce awareness among medical personnel.METHODS： Case description and discussion of a patient presenting to the emergency room after overdose of energy drinks in combination with 3,4-methylenedioxymethamphetamine （MDMA）.RESULTS： Despite best medical efforts, the patient died of fatal cardiac arrhythmias. There is a paucity of information about adverse effects of energy drinks.CONCLUSION： Although energy drinks are widely used, there is a lack of awareness in the population and medical staff about their hazards.
文摘OBJECTIVES: This study was designed to assess the feasibility and safety of a Remote Navigation System(RNS, NaviCath, Haifa, Israel) in which the angioplasty guidewire, the balloon, and the stent are navigated via a computerized system. BACKGROUND: Percutaneous coronary interventions(PCIs) are manually performed under fluoroscopic guidance, requiring lead protection for the operators. A system in which the operator can remotely, safely, and precisely navigate the procedure during PCI would have clear advantages. METHODS: The RNS involves a computer-controlled wire and delivery system navigator. Following preclinical validation, the system was assessed in patients undergoing single-vessel PCI. RESULTS: The study involved 18 patients(age 55.9 years, 16% women). The RNS successfully crossed lesions with the guidewire in 17 patients. The stent was then advanced by the advance/rotate mode and adequately positioned in 15 of 17 cases. Technical malfunction was encountered in three patients in whom the procedure was successfully completed manually. Direct stenting was employed in 10 of 18 patients,pre-dilation in 7 patients, and after-stent balloon dilation in 5 patients. The total fluoroscopy time for 17 RNS patients was compared with the corresponding time of 20 consecutive patients who underwent standard single lesion PCI. Fluoroscopy time was similar for both procedures, with 8.8± 4.8 min with the RNS versus 9.1± 3.5 min with the standard techniques(p=NS). Clinical success was 100% and technical success 94% for the guidewire and 83% for the overall procedure. CONCLUSIONS: The use of the RNS for guidewire, balloon, and stent manipulation during PCI appears safe and feasible for the treatment of patients with coronary stenosis. The system offers operator radiation safety and may enhance precision of stent placement and balloon dilation strategies.
文摘BACKGROUND:Dyspnea is one of the most common complaints facing the emergency medicine physician.Some of the gastrointestinal causes of dyspnea are self-limited and not lifethreatening,yet others are,and early diagnosis and treatment are crucial.METHODS:In this article we presented one of these life-threatening conditions through a clinical description of a patient presenting with acute respiratory distress that was finally diagnosed to be the result of a perforated gastric ulcer.RESULTS:An emergent thoracotomy revealed a small ulcer with perforation in the fundus of the stomach.The patient was transferred after the operation to the intensive care unit and after a prolonged hospitalization discharged home.Biopsies taken from the ulcer showed diffuse inflammation,with no evidence of microorganisms or malignancy.CONCLUSION:Perforation of gastric and duodenal ulcers is a rare yet existing cause of dyspnea and respiratory failure and should be kept in mind by the emergency physician,especially when other more common causes are ruled out.
文摘Objective: To evaluate the effect of inhaled dexamethasone on hospitalization for respiratory syncytial virus (RSV) bronchiolitis. Study design: A double-bli nd, placebo-controlled study compared nebulization of dexamethasone versus nebu lization of 0.9%saline. Both groups were treated with epinephrine nebulizations . Follow-up continued for 3 mo. Patients and methods: Sixty-one infants with b ronchiolitis aged 3 to 12 mo were included. They were randomly allocated to nebu lizations with 0.25 mg dexamethasone every 6 h (group 1) or an equivalent amount of normal saline (group 2). Results: No statistically significant differences w ith respect to clinical score, oxygen saturation, or IV fluid requirement betwee n the groups were noted. Using Kaplan-Meyer’s method, the cumulative proportio n of in-hospital stay was significantly lower in group 1 compared with group 2, mainly in days 5 and 6 post-hospitalization (p < 0.038). A subgroup of prematu rely born children in group 1 had a shorter hospitalization period (6.5 ±1.7 d) compared with group 2 children (9.1 ±1.9) (p < 0.018). Follow-up revealed sim ilar wheeze and hospitalization rates in the two groups. Conclusion: Inhaled dex amethasone may reduce the length of hospitalization among infants with acute vir al bronchiolitis, especially among those born prematurely.
文摘Women with thrombophilia and a history of recurrent pregnancy loss have poor pregnancy outcomes. Prophylaxis with enoxaparin 40 mg/day or 80 mg/day resulted in favorable gestational and neonatal outcomes.
文摘AIM: To evaluate daclatasvir vs telaprevir, each combined with peginterferon alfa-2a/ribavirin(peg IFN/RBV), in treatment-naive hepatitis C virus(HCV) genotype(GT) 1-infected patients.METHODS: In this phase 3, randomized, open-label, noninferiority study, 602 patients were randomly assigned(2:1) to daclatasvir vs telaprevir, stratified by IL28 B rs12979860 host genotype(CC vs non-CC), cirrhosis status(compensated cirrhosis vs no cirrhosis), and HCV GT1 subtype(GT1a vs GT1b). Patients were selected by study inclusion criteria from a total of 793 enrolled patients. Patients received daclatasvir 60 mg once daily or telaprevir 750 mg 3 times daily plus peg IFN/RBV. Daclatasvir recipients received 24 wk of daclatasvir plus peg IFN/RBV; those without an extended rapid virologic response(e RVR; undetectable HCV-RNA at weeks 4 and 12) received an additional 24 wk of peg IFN/RBV. Telaprevir-treated patients received 12 wk of telaprevir plus peg IFN/RBV followed by 12(with e RVR) or 36(no e RVR) wk of peg IFN/RBV. The primary objective was to compare for noninferiority of sustained virologic response rates at posttreatment week 12(SVR12) in GT1b-infected patients. Key secondary objectives were to demonstrate that the rates of anemia(hemoglobin < 10 g/d L) and rashrelated events, through week 12, were lower with daclatasvir + peg IFN/RBV than with telaprevir + peg IFN/RBV among GT1b-infected patients. Resistance testing was performed using population-based sequencing of the NS5 A region for all patients at baseline, and for patients with virologic failure or relapse and HCV-RNA ≥ 1000 IU/m L, to investigate any link between NS5 A polymorphisms associated with daclatasvir resistance and virologic outcome. RESULTS: Patient demographics and disease characteristics were generally balanced across treatment arms; however, there was a higher proportion of black/African Americans in the daclatasvir groups(6.0% and 8.2% in the GT1 b and GT1 a groups, respectively) than in the telaprevir groups(2.2% and 3.0%). Among GT1 binfected patients, daclatasvir plus peg IFN/RBV was noninferior to telaprevir plus peg IFN/RBV for SVR12 [85%(228/268) vs 81%(109/134); difference, 4.3%(95%CI:-3.3% to 11.9%)]. Anemia(hemoglobin < 10 g/d L) was significantly less frequent with daclatasvir than with telaprevir [difference,-29.1%(95%CI:-38.8% to-19.4%)]. Rash-related events were also less common with daclatasvir than with telaprevir, but the difference was not statistically significant. In GT1 ainfected patients, SVR12 was 64.9% with daclatasvir and 69.7% with telaprevir. Among both daclatasvir and telaprevir treatment groups, across GT1b- or GT1a-infected patients, lower response rates were observed in patients with IL28 B non-CC and cirrhosis- factors known to affect response to peg IFN/RBV. Consistent with these observations, a multivariate logistic regression analysis in GT1b-infected patients d e m o n s t ra t e d t h a t S V R 1 2 wa s a s s o c i a t e d w i t h IL28 B host genotype(CC vs non-CC, P = 0.011) and cirrhosis status(absent vs present, P = 0.031). NS5 A polymorphisms associated with daclatasvir resistance(at L28, R30, L31, or Y93) were observed in 17.3% of GT1b-infected patients at baseline; such variants did not appear to be absolute predictors of failure since 72.1% of these patients achieved SVR12 compared with 86.9% without these polymorphisms. Among GT1b-infected patients, treatment was completed by 85.4%(229/268) in the daclatasvir group, and by 85.1%(114/134) in the telaprevir group, and among GT1a-infected patients, by 67.2%(90/134) and 69.7%(46/66), respectively. Discontinuations(of all 3 agents) due to an AE were more frequent with telaprevir than with daclatasvir, whereas discontinuations due to lack of efficacy were more frequent with daclatasvir, due, in part, to differences in futility criteria. CONCLUSION: Daclatasvir plus peg IFN/RBV demonstrated noninferiority to telaprevir plus peg IFN/RBV for SVR12 and was well-tolerated in treatment-naive GT1 binfected patients, supporting the use of daclatasvir with other direct-acting antivirals.
文摘Ectodermal dysplasia/skin fragility syndrome (EDSFS)- (MIM604536) is a newly described autosomal recessive disorder characterized by skin fragility and blistering, palmoplantar keratoderma, abnormal hair growth, nail dystrophy, and occasionally defective sweating. It results from mutations in the PKP1 gene encoding plakophilin 1 (PKP1), which is an important component of stratifying epithelial desmosomes and a nuclear component of many cell types. Our study was performed to further characterize the histopathology of EDSFS in different cutaneous sites with a special emphasis on the hypotrichosis and keratoderma. A total of 4 biopsies were obtained from 2 EDSFS female patients, aged 9 days to 4 years. The biopsies were taken from the blistering skin of the leg and trunk, the hyperkeratotic skin of the sole, and the hypotrichotic scalp. The observed histopathologic features included: widened intercellular spaces, suprabasal intraepidermal clefts and blisters with acantholytic keratinocytes, detachments of the upper epidermal layers due to disadhesion, varying degrees of dyskeratosis thatweremuchmore pronounced in the plantar hyperkeratotic skin, and increased number of catagen- telogen hair follicles. The electron- microscopic observations attributed the disadhesion and acantholysis to reduced numbers of small hypoplastic desmosomes, and the dyskeratosis to the detachment of intracellular keratin filaments from the desmosomes with perinuclear condensation, which might also underlie the plantar keratoderma. The hair follicle findings suggest disturbance in the hair cycle, which might be attributed to disturbed nuclear PKP1 function or result from aberrant desmosomal signaling.
文摘Objective: To establish the unique and common clinical and microscopic characteristics of the alopecias associated with vitamin D-dependent rickets (VDDR) type IIA and with hairless gene mutations. Design: A comparative clinical, histologic, and immunohistochemical study of the alopecias in 6 patients withVDDRIIA and 4 patientswith atrichia with papular lesions (APL) and/or alopecia universalis congenita (AUC) (hereinafter “ APL/AUC” ). Main Outcome Measures: Clinical data were gathered from medical records, personal interviews, and physical examinations. Histologic and immunohistochemical studies were performed on 6 scalp punch biopsy specimens from each of the 2 studied groups. Results: The alopecias in VDDR IIA and APL/AUC showed similar clinical, histologic, and immunohistochemical features. The clinical presentation of the VDDR alopecia resembled either the APL phenotype (ie, with papules and milia) or the AUC phenotype (without papules and milia). The main histologic findings included void infundibula; absence of the lower two thirds of the hair follicles, often replaced by vertically oriented irregular epithelial structures or epithelial cysts; irregular epithelial structures, often with small cysts in the middle and lower dermis; and small, medium, and large keratinizing cysts at all levels of the dermis. The larger epithelial cysts in the upper dermis stained positively for cytokeratin (CK) 10, which suggests an infundibular derivation, whereas the remaining irregular epithelial structures and cysts in themiddle and lower dermis stained positivelymost frequently forCK17, CK19, andCD34,which suggests an outer root sheath derivation. Conclusions: The alopecias associated with VDDR IIA and with hairless gene mutations show striking clinical and microscopic similarities. Disintegration of the lower two thirds of the hair follicles seems to be the underlying defect, and a common pathogenetic pathwaymight be involved.
文摘Background. Prolidase deficiency is a complex disease characterized by various skin manifestations accompanied by mental retardation, facial dysmorphism and susceptibility to pyogenic infections. Methods. We assessed a patient presenting a peculiar phenotype combining manifestations of prolidase deficiency with features typical of hyper-IgE syndrome. Mutation analysis was performed using direct PCR amplification and PCR restriction fragment length polymorphism analysis. Results. We identified a novel homozygous recessive mutation in the PEPD gene, which was found to segregate in the family of the patient with the disease and was not found in a panel of DNA samples representative of all major Druze families living in northern Israel. Discussion. Our results suggest that prolidase deficiency associated with hyper-IgE syndrome, a rare disorder, can be caused by mutations in PEPD.
文摘Objective： Primary uterine leiomyosarcomas （ULMS） are rare, and the optimal treatment is controversial. We aimed to assess the outcome and prognostic factors in a multicenter population of women treated for primary ULMS. Methods： We retrospectively collected data of 110 women treated in 19 institutions of the Rare Cancer Network （RCN）. Inclusion criteria consisted of a pathology report confirming the diagnosis of ULMS, aged 18-80 years, complete International Federation of Gynecology and Obstetrics （FIGO） stage information, complete information on treatment, and a minimum follow-up of 6 months. Local control （LC） and locoregional control （LRC）, overall survival （OS） and disease-free survival （DFS） rates were computed using the Kaplan-Meier method. Univariate analysis was implemented using the log rank test, and multivariate analysis using the Cox model. Results： All patients underwent surgery. Seventy-five patients （68%） received adjuvant radiotherapy （RT）, including brachytherapy in 18 （I 6%）. Seventeen patients （15 %） received adjuvant chemotherapy. Median follow-up was 58 （range, 6-240） months. Five-year OS and DFS rates were 50% and 34%, and LC and LRC rates were 88% and 72%, respectively. On multivariate analysis, independent favorable prognostic factors were younger age, FIGO stage I, small tumor size, previous uterine disease, and no vascular invasion for OS and DFS. FIGO stage was the only favorable factor influencing LRC. Adjuvant local or systemic treatments did not improve the outcomes. Eight patients treated with RT presented a grade 3 acute toxicity, and only one patient with grade 3 late toxicity. Conclusions： In this large population of primary ULMS patients, we found good results in terms of LC and LRC. Nevertheless, OS remains poor, mainly due to the occurrence of distant metastases. An early diagnosis seemed to improve the prognosis of the patients. Adjuvant local or systemic treatments, or more aggressive surgical procedures such as the Wertheim procedure, did not seem to impact the outcome.
