Usher Syndrome(USH)is the most common deaf-blind syndrome,affecting approximately 1 in 6000 people in the deaf population.This genetic condition is characterized by a combination of hearing loss(HL),retinitis pigmento...Usher Syndrome(USH)is the most common deaf-blind syndrome,affecting approximately 1 in 6000 people in the deaf population.This genetic condition is characterized by a combination of hearing loss(HL),retinitis pigmentosa,and,in some cases,vestibular areflexia.Among the subtypes of USH,USH type 1 is considered the most severe form,presenting profound bilateral congenital deafness,vestibular areflexia,and early onset RP.USH type 2 is the most common form,exhibiting congenital moderate to severe HL for low frequencies and severe to profound HL for high frequencies.Conversely,type 3 is the rarest,initially manifesting mild symptoms during childhood that become more prominent in the first decades of life.The dual impact of USH on both visual and auditory senses significantly impairs patients'quality of life,restricting their daily activities and interactions with society.To date,9 genes have been confirmed so far for USH:MYO7A,USH1C,CDH23,PCDH15,USH1G,USH2A,ADGRV1,WHRN and CLRN1.These genes are inherited in an autosomal recessive manner and encode proteins expressed in the inner ear and retina,leading to functional loss.Although non-genetic methods can assist in patient triage and disease extension evaluation,genetic and molecular tests play a pivotal role in providing genetic counseling,enabling appropriate gene therapy,and facilitating timely cochlear implantation(CI).The CRISPR/Cas9 system and viral-based gene replacement therapy have recently emerged as highly promising techniques for treating USH.Regarding drug therapy,PTC-124 and Nb54 have been identified as promising drug interventions for genetic HL in USH.Simultaneously,CI has proven to be critical in the restoration of hearing.This review aims to summarize the genetic and molecular diagnosis of USH and highlight the importance of early diagnosis in Cuzzuol BR et al.Diagnosis and current treatments of USH WJO https://www.wjgnet.com 2 January 19,2024 Volume 11 Issue 1 guiding appropriate treatment strategies and improving patient prognosis.展开更多
Objective: To study the value of clonal analysis to the early diagnosis of myelodysplastic syndrome (MDS). Methods: Four types of clonal analyses were performed on the bone marrow samples from 50 patients suspected of...Objective: To study the value of clonal analysis to the early diagnosis of myelodysplastic syndrome (MDS). Methods: Four types of clonal analyses were performed on the bone marrow samples from 50 patients suspected of MDS: (1) Conventional Cytogenetics (CC) for clonal chromosomal abnormalities; (2) BrdU-Sister Chromatid Differentiation (BrdU-SCD) for cell cycle kinetics; (3) Fluorescence in Situ Hybridization (FISH) for trisomy 8; (4) Polymerase chain reaction-single strand conformation polymorphism (PCR-SSCP) for N-ras mutation. Results: The diagnosis of forty-three patients was compatible with the FAB criteria for MDS. The other seven cases didn’t meet the FAB criteria, with only one lineage of dyspoiesis or with no obvious dysplastic changes. Among these seven cases, two were morphologically diagnosed with suspicious refractory anemia, one with sideroblastic anemia, one with leukemoid reaction, one with hypercellular anemia and two with chronic aplastic anemia. Clonal analyses of the 7 patients showed that six cases had clonal karyotype abnormalities, four had prolonged cell cycle patterns, four had trisomy 8 of different proportions and one had mutation of the exon 1 of N-RAS. Thus, they were revaluated as MDS patients. Conclusion: The untypical MDS patients with one lineage dyspoiesis or without obvious dysplastic changes can be diagnosed early by combining multiple clonal analysis techniques such as CC, SCD, FISH and PCR-SSCR.展开更多
Myelodysplastic syndromes(MDS)are highly heterogeneous myeloid neoplasms,and a large number of patients are difficult to diagnose and classify by blood and bone marrow examination.As a surface marker of granulocyte,st...Myelodysplastic syndromes(MDS)are highly heterogeneous myeloid neoplasms,and a large number of patients are difficult to diagnose and classify by blood and bone marrow examination.As a surface marker of granulocyte,studies have shown CD10 can be used to define the degree of granulocyte maturation in MDS patients.However,whether it can be used for differential diagnosis of MDS and other hematological diseases remains inconclusive.To explore the value of CD10 for differential diagnosis of MDS,60 newly diagnosed MDS,20 aplastic anemia(AA)patients,and 35 iron-deficient anemia(IDA)patients were selected for this study.Bone marrow(BM)specimens were processed for surface marker analysis and labeled with pre-conjugated monoclonal antibodies.Stained cells were detected by flow cytometry.Our results indicated that CD10-positive granulocytes were significantly decreased in BM of MDS patients than AA and IDA patients,and the level of CD10-positive mature granulocytes was not associated with the clinical stages of malignancy.Receiver operating characteristic(ROC)areas under the curve(AUC)of CD10-positive granulocytes was 0.86 and 0.85,respectively,in MDS patients than the IDA group and AA group with good specificity and sensitivity.Further,CD10-positive granulocytes were increased after effective treatment.In conclusion,we found the decrease in CD10-positive granulocytes has a differential diagnostic value of MDS.展开更多
Hepatorenal syndrome with acute kidney injury(HRS-AKI)is a form of rapidly progressive kidney dysfunction in patients with decompensated cirrhosis and/or acute severe liver injury such as acute liver failure.Current d...Hepatorenal syndrome with acute kidney injury(HRS-AKI)is a form of rapidly progressive kidney dysfunction in patients with decompensated cirrhosis and/or acute severe liver injury such as acute liver failure.Current data suggest that HRS-AKI occurs secondary to circulatory dysfunction characterized by marked splanchnic vasodilation,leading to reduction of effective arterial blood volume and glomerular filtration rate.Thus,volume expansion and splanchnic vasoconstriction constitute the mainstay of medical therapy.However,a significant proportion of patients do not respond to medical management.These patients often require renal replacement therapy and may be eligible for liver or combined liver-kidney transplantation.Although there have been advances in the management of patients with HRS-AKI including novel biomarkers and medications,better-calibrated studies,more widely available biomarkers,and improved prognostic models are sorely needed to further improve diagnosis and treatment of HRS-AKI.展开更多
The pathogenesis of myelodysplastic syndrome(MDS)may be related to the abnormal expression of microRNAs(miRNAs),which could influence the differentiation capacity of mesenchymal stem cells(MSCs)towards adipogenic and ...The pathogenesis of myelodysplastic syndrome(MDS)may be related to the abnormal expression of microRNAs(miRNAs),which could influence the differentiation capacity of mesenchymal stem cells(MSCs)towards adipogenic and osteogenic lineages.In this study,exosomes from bone marrow plasma were successfully extracted and identified.Assessment of miR-103-3p expression in exosomes isolated from BM in 34 MDS patients and 10 controls revealed its 0.52-fold downregulation in patients with MDS compared with controls(NOR)and was downregulated 0.55-fold in MDS-MSCs compared with NOR-MSCs.Transfection of MDS-MSCs with the miR-103-3p mimic improved osteogenic differentiation and decreased adipogenic differentiation in vitro,while inhibition of miR-103-3p showed the opposite results in NOR-MSCs.Thus,the expression of miR-103-3p decreases in MDS BM plasma and MDS-MSCs,significantly impacting MDS-MSCs differentiation.The miR-103-3p mimics may boost MDS-MSCs osteogenic differentiation while weakening lipid differentiation,thereby providing possible target for the treatment of MDS pathogenesis.展开更多
BACKGROUND Patients with trisomy 8 consistently present with myeloid neoplasms and/or auto-inflammatory syndrome.A possible link between myelodysplastic syndromes(MDS)with trisomy 8(+8-MDS)and inflammatory disorders i...BACKGROUND Patients with trisomy 8 consistently present with myeloid neoplasms and/or auto-inflammatory syndrome.A possible link between myelodysplastic syndromes(MDS)with trisomy 8(+8-MDS)and inflammatory disorders is well recognized,several cases having been reported.However,inflammatory disorders in patients without MDS have been largely overlooked.Generally,Behçet's disease is the most common type in+8-MDS.However,inflammatory disorders with pulmonary involvement are less frequent,and no effective treatment has been established.CASE SUMMARY A 27-year-old man with recurrent fever,fatigue for>2 mo,and unconsciousness for 1 day was admitted to our emergency department with a provisional diagnosis of severe pneumonia.Vancomycin and imipenem were administered and sputum collected for metagenomic next-generation sequencing.Epstein–Barr virus and Mycobacterium kansasii were detected.Additionally,chromosomal analysis showed duplications on chromosome 8.Two days later,repeat metagenomic next-generation sequencing was performed with blood culture.Cordyceps portugal,M.kansasii,and Candida portugal were detected,and duplications on chromosome 8 confirmed.Suspecting hematological disease,we aspirated a bone marrow sample from the iliac spine,examination of which showed evidence of infection.We added fluconazole as further antibiotic therapy.Seven days later,the patient’s condition had not improved,prompting addition of methylprednisolone as an anti-inflammatory agent.Fortunately,this treatment was effective and the patient eventually recovered.CONCLUSION Severe inflammatory disorders with pulmonary involvement can occur in patients with trisomy 8.Methylprednisolone may be an effective treatment.展开更多
BACKGROUND Myelodysplastic syndrome(MDS)is a hematological neoplasm,and an increase in myeloblasts is representative of leukemic hematopoiesis in advanced MDS.Lowrisk MDS usually exhibits deranged autoimmunity resembl...BACKGROUND Myelodysplastic syndrome(MDS)is a hematological neoplasm,and an increase in myeloblasts is representative of leukemic hematopoiesis in advanced MDS.Lowrisk MDS usually exhibits deranged autoimmunity resembling that of aplastic anemia(AA),whereas advanced MDS is characterized by a phenotype of immune exhaustion.MDS can be normo/hyperplastic or hypoplastic.Generally,bone marrow cellularity and myeloblasts increase with disease progression.Transformation from advanced MDS to AA-like syndrome with leukemic cell regression has not previously been reported.CASE SUMMARY A middle-aged Chinese woman had a 4-year history of leukocytopenia.Six months prior to admission,the patient developed gradually worsening fatigue and performance status.The leukocytopenia further progressed.She was diagnosed with MDS with excess blasts-2 based on increased bone marrow cellularity and an increased percentage of myeloblasts on marrow and blood smears,an increased percentage of cluster of differentiation(CD)34+CD33+progenitors in immunotyping analysis,a normal karyotype in cytogenetic analysis,and the identification of somatic mutations in CBL,KMT2D and NF1 in molecular analysis.Initially,neutropenia was the predominant hematological abnormality,with mild anemia and thrombocytosis,and the degree of fatigue was far more severe than the degree of anemia.In the following months,the patient experienced several febrile episodes.Intravenous antibiotic treatments were able to control the febrile episodes,but the elevated inflammatory indices persisted.The hematological parameters dramatically fluctuated with the waxing and waning of the inflammatory episodes.With recurrent flares of the inflammatory condition,agranulocytosis and severe anemia developed,with mild thrombocytopenia.During the patient’s hospitalization,computed tomography(CT)scans revealed the presence of extensive inflammatory lesions involving the lungs,mediastinum,pleura,gastrointestinal tract,peritoneum and urinary tract,with imaging features suggestive of the reactivation of disseminated tuberculosis.Reevaluation of the bone marrow smears revealed that the cellularity became hypoplastic,and the leukemic cells regressed,suggesting that both normal and leukemic hematopoiesis had been heavily suppressed.Immunological analysis of the bone marrow samples revealed a decreased percentage of CD34+cells and an immunological signature resembling that of severe AA(SAA),confirming the regression of the leukemic cells by autoimmune-mediated attacks.The patient demonstrated resistance to multiple drugs,including antituberculotics,recombinant human granulocyte colony-stimulating factor,broad-spectrum antibiotics,voriconazole,ganciclovir,immune suppressants,eltrombopag and intravenous immunoglobulin,which further worsened the hematological injury and patient’s performance status.The patient eventually died of overwhelming infection and multidrug resistance.CONCLUSION Advanced MDS can transform to aplastic cytopenia with leukemic cell regression and an immunological signature of SAA during inflammatory flare-ups.展开更多
BACKGROUND Myelodysplastic syndrome(MDS)is caused by malignant proliferation and ineffective hematopoiesis.Oncogenic somatic mutations and increased apoptosis,necroptosis and pyroptosis lead to the accumulation of ear...BACKGROUND Myelodysplastic syndrome(MDS)is caused by malignant proliferation and ineffective hematopoiesis.Oncogenic somatic mutations and increased apoptosis,necroptosis and pyroptosis lead to the accumulation of earlier hematopoietic progenitors and impaired productivity of mature blood cells.An increased percentage of myeloblasts and the presence of unfavorable somatic mutations are signs of leukemic hematopoiesis and indicators of entrance into an advanced stage.Bone marrow cellularity and myeloblasts usually increase with disease progression.However,aplastic crisis occasionally occurs in advanced MDS.CASE SUMMARY A 72-year-old male patient was definitively diagnosed with MDS with excess blasts-1(MDS-EB-1)based on an increase in the percentages of myeloblasts and cluster of differentiation(CD)34+hematopoietic progenitors and the identification of myeloid neoplasm-associated somatic mutations in bone marrow samples.The patient was treated with hypomethylation therapy and was able to maintain a steady disease state for 2 years.In the treatment process,the advanced MDS patient experienced an episode of progressive pancytopenia and bone marrow aplasia.During the aplastic crisis,the bone marrow was infiltrated with sparsely distributed atypical lymphocytes.Surprisingly,the leukemic cells disappeared.Immunological analysis revealed that the atypical lymphocytes expressed a high frequency of CD3,CD5,CD8,CD16,CD56 and CD57,suggesting the activation of autoimmune cytotoxic T-lymphocytes and natural killer(NK)/NKT cells that suppressed both normal and leukemic hematopoiesis.Elevated serum levels of inflammatory cytokines,including interleukin(IL)-6,interferon-gamma(IFN-γ)and tumor necrosis factor-alpha(TNF-α),confirmed the deranged type I immune responses.This morphological and immunological signature led to the diagnosis of severe aplastic anemia secondary to large granule lymphocyte leukemia.Disseminated tuberculosis was suspected upon radiological examinations in the search for an inflammatory niche.Antituberculosis treatment led to reversion of the aplastic crisis,disappearance of the atypical lymphocytes,increased marrow cellularity and 2 mo of hematological remission,providing strong evidence that disseminated tuberculosis was responsible for the development of the aplastic crisis,the regression of leukemic cells and the activation of CD56+atypical lymphocytes.Reinstitution of hypomethylation therapy in the following 19 mo allowed the patient to maintain a steady disease state.However,the patient transformed the disease phenotype into acute myeloid leukemia and eventually died of disease progression and an overwhelming infectious episode.CONCLUSION Disseminated tuberculosis can induce CD56+lymphocyte infiltration in the bone marrow and in turn suppress both normal and leukemic hematopoiesis,resulting in the development of aplastic crisis and leukemic cell regression.展开更多
BACKGROUND Sotos syndrome is an autosomal dominant disorder,whereas attention-deficit/hyperactivity disorder(ADHD)is a neurodevelopmental condition.This report aimed to summarize the clinical and genetic features of a...BACKGROUND Sotos syndrome is an autosomal dominant disorder,whereas attention-deficit/hyperactivity disorder(ADHD)is a neurodevelopmental condition.This report aimed to summarize the clinical and genetic features of a pediatric case of Soros syndrome and ADHD in a child exhibiting precocious puberty.CASE SUMMARY The patient presented with accelerated growth and advanced skeletal maturation;however,she lacked any distinct facial characteristics related to specific genetic disorders.Genetic analyses revealed a paternally inherited heterozygous synonymous mutation[c.4605C>T(p.Arg1535Arg)].Functional analyses suggested that this mutation may disrupt splicing,and bioinformatics analyses predicted that this mutation was likely pathogenic.After an initial diagnosis of Sotos syndrome,the patient was diagnosed with ADHD during the follow-up period at the age of 8 years and 7 months.CONCLUSION The potential for comorbid ADHD in Sotos syndrome patients should be considered to avoid the risk of a missed diagnosis.展开更多
Amniotic band syndrome is an acquired embryo-fetopathy. It is rare and is characterized by malformations mainly affecting the limbs but also the skull, face and thoraco-abdominal axis. Its etiopathogenesis remains poo...Amniotic band syndrome is an acquired embryo-fetopathy. It is rare and is characterized by malformations mainly affecting the limbs but also the skull, face and thoraco-abdominal axis. Its etiopathogenesis remains poorly understood. Its diagnosis is essentially clinical and is classically based on the existence of signs such as furrows, amputations and pseudosyndactyly. To show the importance of antenatal diagnosis in resource-limited countries, we report the case of two newborns, one premature at 31 weeks and the other at term, in whom amniotic band syndrome was discovered incidentally at birth. It involved an amputation of the right leg for both cases. The premature baby was born in a context of neonatal sepsis and will succumb to the latter while the 2nd case was released from the hospital alive. Imaging examinations to search for probable congenital malformations could only be carried out for the 2nd case and no accessible congenital malformation had been identified. And as management of the disease, only psychological support to the parents was provided for the 2 cases. The antenatal discovery of a case of amniotic band syndrome in countries with low technical capacity such as Burundi should push clinicians to think in time about treatment options.展开更多
Introduction: Prostate cancer is one of the most common cancers in men. In cases of suspected locally advanced disease or lymph node or bone metastases, thoraco-abdomino-pelvic CT is still useful for detecting viscera...Introduction: Prostate cancer is one of the most common cancers in men. In cases of suspected locally advanced disease or lymph node or bone metastases, thoraco-abdomino-pelvic CT is still useful for detecting visceral metastases. In the course of this extension work-up, other abnormalities may be discovered by chance, which had previously remained silent, and which could be diagnosed and managed in childhood, hence the interest of presenting a case of incidental finding of pyeloureteral junction syndrome during extension workup for prostatic adenocarcinoma at Yaounde Central Hospital. Observation: A 72-year-old patient presented to the department with acute urinary retention. The clinical examination, with an empty bladder, and in particular the digital rectal exam (DRE), was in favor of malignant prostatic hypertrophy. A workup was ordered, including a total PSA returned to 61.3 ng/ml (PSA performed one week after the episode of acute urinary retention) with cytobacteriological examination of sterile urine. Renal function was slightly impaired, with creatinemia at 14 ng/ml. Renal and vesico-prostatic ultrasound revealed a 57 g prostate with regular, clean contours and a polycystic right kidney. A prostate biopsy was indicated, which revealed a histopathological aspect in favor of a prostatic adenocarcinoma ISUP 1. An extension work-up including a thoraco-abdomino-pelvic CT scan revealed no signs of local or distant secondary localization, but a pyeloureteral junction syndrome with significant hydronephrosis, parenchymal destruction and compensatory hypertrophy of the contralateral kidney was found. Conclusion: The prostate cancer extension work-up revealed a pathology that can be diagnosed early. It is therefore important to reinforce prenatal and natal screening, which will enable malformative uropathies to be identified early and corrected in time to preserve patients’ renal function. Furthermore, we must be careful in the ultrasound diagnosis of pyeloureteral junction syndrome.展开更多
Irritable bowel syndrome (IBS) is a chronic and debilitating functional gastrointestinal disorder that affects 9%-23% of the population across the world. The percentage of patients seeking health care related to IBS a...Irritable bowel syndrome (IBS) is a chronic and debilitating functional gastrointestinal disorder that affects 9%-23% of the population across the world. The percentage of patients seeking health care related to IBS approaches 12% in primary care practices and is by far the largest subgroup seen in gastroenterology clinics. It has been well documented that these patients exhibit a poorer quality of life and utilize the health care system to a greater degree than patients without this diagnosis. The pathophysiology of IBS is not clear. Many theories have been put forward, but the exact cause of IBS is still uncertain. According to the updated ROME III criteria, IBS is a clinical diagnosis and presents as one of the three predominant subtypes: (1) IBS with constipation (IBS-C); (2) IBS with diarrhea (IBS-D); and (3) mixed IBS (IBS-M); former ROME definitions refer to IBS-M as alternating IBS (IBS-A). Across the IBS subtypes, the presentation of symptoms may vary among patients and change over time. Patients report the most distressing symptoms to be abdominal pain, straining, myalgias, urgency, bloating and feelings of serious illness. The complexity and diversity of IBS presentation makes treatment difficult. Although there are reviews and guidelines for treating IBS, they focus on the efficacy of medications for IBS symptoms using high-priority endpoints, leaving those of lower priority largely unreported. Therefore, the aim of this review is to provide a comprehensive evidence-based review of the diagnosis, pathogenesis and treatment to guide clinicians diagnosing and treating their patients.展开更多
Irritable bowel syndrome (IBS) is the most frequently diagnosed functional gastrointestinal disorder in primary and secondary care. It is characterised by abdominal discomfort, pain and changes in bowel habits that ca...Irritable bowel syndrome (IBS) is the most frequently diagnosed functional gastrointestinal disorder in primary and secondary care. It is characterised by abdominal discomfort, pain and changes in bowel habits that can have a serious impact on the patient’s quality of life. The pathophysiology of IBS is not yet completely clear. Genetic, immune, environmental, inflammatory, neurological and psychological factors, in addition to visceral hypersensitivity, can all play an important role, one that most likely involves the complex interactions between the gut and the brain (gut-brain axis). The diagnosis of IBS can only be made on the basis of the symptoms of the Rome III criteria. Because the probability of organic disease in patients fulfilling the IBS criteria is very low, a careful medical history is critical and should pay particular attention to the possible comorbidities. Nevertheless, the severity of the patient’s symptoms or concerns sometimes compels the physician to perform useless and/or expensive diagnostic tests, transforming IBS into a diagnosis of exclusion. The presence of alarming symptoms (fever, weight loss, rectal bleeding, significant changes in blood chemistry), the presence of palpable abdominal masses, any recent onset of symptoms in patient aged over 50 years, the presence of symptoms at night, and a familial history of celiac disease, colorectal cancer and/or inflammatory bowel diseases all warrant investigation. Treatment strategies are based on the nature and severity of the symptoms, the degree of functional impairment of the bowel habits, and the presence of psychosocial disorders. This review examines and discusses the pathophysiological aspects and the diagnostic and therapeutic approaches available for patients with symptoms possibly related to IBS, pointing out controversial issues and the strengths and weaknesses of the current knowledge.展开更多
Budd-Chiari syndrome is a congestive hepatopathy caused by blockage of hepatic veins. This syndrome occurs in 1/100 000 in the general population. Hypercoagulable state could be identified in 75% of the patients; more...Budd-Chiari syndrome is a congestive hepatopathy caused by blockage of hepatic veins. This syndrome occurs in 1/100 000 in the general population. Hypercoagulable state could be identified in 75% of the patients; more than one etiologic factor may play a role in 25% of the patients. Primary myeloproliferative diseases are the leading cause of the disease. Two of the hepatic veins must be blocked for clinically evident disease. Liver congestion and hypoxic damage of hepatocytes eventually result in predominantly centrilobular fibrosis. Doppler ultrasonography of the liver should be the initial diagnostic procedure. Hepatic venography is the reference procedure if required. Additionally liver biopsy may be helpful for differential diagnosis. The prognosis of the chronic form is acceptable compared to other chronic liver diseases.展开更多
Presented in this paper is our experience in the diagnosis and management of abdominal compartment syndrome during severe acute pancreatitis. On the basis of the history of severe acute pancreatitis, after effective ...Presented in this paper is our experience in the diagnosis and management of abdominal compartment syndrome during severe acute pancreatitis. On the basis of the history of severe acute pancreatitis, after effective fluid resuscitation, if patients developed renal, pulmonary and cardiac insufficiency after abdominal expansion and abdominal wall tension, ACS should be considered. Cystometry could be performed to confirm the diagnosis. Emergency decompressive celiotomy and temporary abdominal closure with a 3 liter sterile plastic bag must be performed. It is also critical to prevent reperfusion syndrome. In 23 cases of ACS, 18 cases received emergency decompressive celiotomy and 5 cases did not. In the former, 3 patients died (16.7 %) while in the later, 4 (80%) died. Total mortality rate was 33.3% (7/21). In 7 death cases, 4 patients developed acute obstructive suppurative cholangitis (AOSC). All the patients who received emergency decompressive celiotomy 5 h after confirmation of ACS survived. The definitive abdominal closure took place mostly 3 to 5 days after emergency decompressive celiotomy, with longest time being 8 days. 6 cases of ACS at infection stage were all attributed to infected necrosis in abdominal cavity and retroperitoneum. ACS could occur in SIRS stage and infection stage during SAP, and has different pathophysiological basis. Early diagnosis, emergency decompressive celiotomy and temporary abdominal closure with a 3L sterile plastic bag are the keys to the management of the condition.展开更多
The myelodysplastic/myeloproliferative neoplasms(MDS/MPNs) are a unique group of hematologic malignancies characterized by concomitant myelodysplastic and myeloproliferative features. According to the 2008 WHO classif...The myelodysplastic/myeloproliferative neoplasms(MDS/MPNs) are a unique group of hematologic malignancies characterized by concomitant myelodysplastic and myeloproliferative features. According to the 2008 WHO classification, the category includes atypical chronic myeloid leukemia(a CML), chronic myelomonocytic leukemia(CMML), juvenile myelomonocytic leukemia(JMML), MDS/MPN-unclassifiable(MDS/MPN-U), and the provisional entity refractory anemia with ring sideroblasts and thrombocytosis(RARS-T). Although diagnosis currently remains based on clinicopathologic features, the incorporation of nextgeneration platforms has allowed for the recent molecular characterization of these diseases which has revealed unique and complex mutational profiles that support their distinct biology and is anticipated to soon play an integral role in diagnosis,prognostication, and treatment. Future goals of research should include the development of disease-modifying therapies, and further genetic understanding of the category will likely form the foundation of these efforts.展开更多
AIM: To validate 4-sample lactose hydrogen breath testing(4SLHBT) compared to standard 13-sample LHBT in the clinical setting.METHODS: Irritable bowel syndrome patients with diarrhea(IBS-D) and healthy volunteers(HVs)...AIM: To validate 4-sample lactose hydrogen breath testing(4SLHBT) compared to standard 13-sample LHBT in the clinical setting.METHODS: Irritable bowel syndrome patients with diarrhea(IBS-D) and healthy volunteers(HVs) were enrolled and received a 10 g, 20 g, or 40 g doselactose hydrogen breath test(LHBT) in a randomized, double-blinded, controlled trial. The lactase gene promoter region was sequenced. Breath samples and symptoms were acquired at baseline and every 15 min for 3 h(13 measurements). The detection rates of lactose malabsorption(LM) and lactose intolerance(LI) for a 4SLHBT that acquired four measurements at 0, 90, 120, and 180 min from the same data set were compared with the results of standard LHBT.RESULTS: Sixty IBS-D patients and 60 HVs were studied. The genotype in all participants was C/C-13910. LM and LI detection rates increased with lactose dose from 10 g, 20 g to 40 g in both groups(P < 0.001). 4SLHBT showed excellent diagnostic concordance with standard LHBT(97%-100%, Kappa 0.815-0.942) with high sensitivity(90%-100%) and specificity(100%) at all three lactose doses in both groups.CONCLUSION: Reducing the number of measurements from 13 to 4 samples did not significantly impact on the accuracy of LHBT in health and IBS-D. 4SLHBT is a valid test for assessment of LM and LI in clinical practice.展开更多
AIM To evaluate factors associated with Clostridium difficile infection (CDI) and outcomes of CDI in the myelodysplastic syndrome(MDS) and acute myeloid leukemia (AML) population.METHODS After IRB approval,all MDS/AML...AIM To evaluate factors associated with Clostridium difficile infection (CDI) and outcomes of CDI in the myelodysplastic syndrome(MDS) and acute myeloid leukemia (AML) population.METHODS After IRB approval,all MDS/AML patients hospitalized at the University of Maryland Greenebaum Comprehensive Cancer Center between August 2011 and December 2013 were identified.Medical charts were reviewed for demographics,clinical information,development of CDI,complications of CDI,and mortality.Patients with CDI,defined as having a positive stool PCR done for clinical suspicion of CDI,were compared to those without CDI in order to identify predictors of disease.A t-test was used for comparison of continuous variables and chisquare or Fisher's exact tests were used for categorical variables,as appropriate.RESULTS Two hundred and twenty-three patients (60.1% male,mean age 61.3 years,13% MDS,87% AML) had 594 unique hospitalizations during the study period.Thirtyfour patients (15.2%) were diagnosed with CDI.Factors significantly associated with CDI included lower albumin at time of hospitalization (P < 0.0001),prior diagnosis of CDI (P < 0.0001),receipt of cytarabine-based chemotherapy (P = 0.015),total days of neutropenia (P = 0.014),and total days of hospitalization (P = 0.005).Gender (P = 0.10),age (P = 0.77),proton-pump inhibitor use (P = 0.73),receipt of antibiotics (P = 0.66),and receipt of DNA hypomethylating agent-based chemotherapy (P = 0.92) were not significantly associated with CDI.CONCLUSION CDI is common in the MDS/AML population.Factors significantly associated with CDI in this population include low albumin,prior CDI,use of cytarabine-based chemotherapy,and prolonged neutropenia.In this study,we have identified a subset of patients in which prophylaxis studies could be targeted.展开更多
Myelodysplastic syndromes have increased in frequency and incidence in the American population, but patient prognosis has not significantly improved over the last decade. Such improvements could be realized if biomark...Myelodysplastic syndromes have increased in frequency and incidence in the American population, but patient prognosis has not significantly improved over the last decade. Such improvements could be realized if biomarkers for accurate diagnosis and prognostic stratification were successfully identified. In this study, we propose a method that associates two state-of-the-art array technologies-single nucleotide polymorphism (SNP) array and gene expression array-with gene motifs considered transcription factor -binding sites (TFBS). We are particularly interested in SNP-containing motifs introduced by genetic variation and mutation as TFBS. The potential regulation of SNP-containing motifs affects only when certain mutations occur. These motifs can be identified from a group of co-expressed genes with copy number variation. Then, we used a sliding window to identify motif candidates near SNPs on gene sequences. The candidates were filtered by coarse thresholding and fine statistical testing. Using the regression-based LARS-EN algorithm and a level-wise sequence combination procedure, we identified 28 SNP-containing motifs as candidate TFBS. We confirmed 21 of the 28 motifs with ChIP-chip fragments in the TRANSFAC database. Another six motifs were validated by TRANSFAC via searching binding fragments on coregulated genes. The identified motifs and their location genes can be considered potential biomarkers for myelodysplastic syndromes. Thus, our proposed method, a novel strategy for associating two data categories, is capable of integrating information from different sources to identify reliable candidate regulatory SNP-containing motifs introduced by genetic variation and mutation.展开更多
文摘Usher Syndrome(USH)is the most common deaf-blind syndrome,affecting approximately 1 in 6000 people in the deaf population.This genetic condition is characterized by a combination of hearing loss(HL),retinitis pigmentosa,and,in some cases,vestibular areflexia.Among the subtypes of USH,USH type 1 is considered the most severe form,presenting profound bilateral congenital deafness,vestibular areflexia,and early onset RP.USH type 2 is the most common form,exhibiting congenital moderate to severe HL for low frequencies and severe to profound HL for high frequencies.Conversely,type 3 is the rarest,initially manifesting mild symptoms during childhood that become more prominent in the first decades of life.The dual impact of USH on both visual and auditory senses significantly impairs patients'quality of life,restricting their daily activities and interactions with society.To date,9 genes have been confirmed so far for USH:MYO7A,USH1C,CDH23,PCDH15,USH1G,USH2A,ADGRV1,WHRN and CLRN1.These genes are inherited in an autosomal recessive manner and encode proteins expressed in the inner ear and retina,leading to functional loss.Although non-genetic methods can assist in patient triage and disease extension evaluation,genetic and molecular tests play a pivotal role in providing genetic counseling,enabling appropriate gene therapy,and facilitating timely cochlear implantation(CI).The CRISPR/Cas9 system and viral-based gene replacement therapy have recently emerged as highly promising techniques for treating USH.Regarding drug therapy,PTC-124 and Nb54 have been identified as promising drug interventions for genetic HL in USH.Simultaneously,CI has proven to be critical in the restoration of hearing.This review aims to summarize the genetic and molecular diagnosis of USH and highlight the importance of early diagnosis in Cuzzuol BR et al.Diagnosis and current treatments of USH WJO https://www.wjgnet.com 2 January 19,2024 Volume 11 Issue 1 guiding appropriate treatment strategies and improving patient prognosis.
文摘Objective: To study the value of clonal analysis to the early diagnosis of myelodysplastic syndrome (MDS). Methods: Four types of clonal analyses were performed on the bone marrow samples from 50 patients suspected of MDS: (1) Conventional Cytogenetics (CC) for clonal chromosomal abnormalities; (2) BrdU-Sister Chromatid Differentiation (BrdU-SCD) for cell cycle kinetics; (3) Fluorescence in Situ Hybridization (FISH) for trisomy 8; (4) Polymerase chain reaction-single strand conformation polymorphism (PCR-SSCP) for N-ras mutation. Results: The diagnosis of forty-three patients was compatible with the FAB criteria for MDS. The other seven cases didn’t meet the FAB criteria, with only one lineage of dyspoiesis or with no obvious dysplastic changes. Among these seven cases, two were morphologically diagnosed with suspicious refractory anemia, one with sideroblastic anemia, one with leukemoid reaction, one with hypercellular anemia and two with chronic aplastic anemia. Clonal analyses of the 7 patients showed that six cases had clonal karyotype abnormalities, four had prolonged cell cycle patterns, four had trisomy 8 of different proportions and one had mutation of the exon 1 of N-RAS. Thus, they were revaluated as MDS patients. Conclusion: The untypical MDS patients with one lineage dyspoiesis or without obvious dysplastic changes can be diagnosed early by combining multiple clonal analysis techniques such as CC, SCD, FISH and PCR-SSCR.
基金the National Natural Science Foundation of China(81670179)Research Fund Project of Anhui Medical University(No.2018xkj026)National Natural Science Foundation Incubation Project of the Second Hospital of Anhui Medical University(Grant No.2019GQFY11).
文摘Myelodysplastic syndromes(MDS)are highly heterogeneous myeloid neoplasms,and a large number of patients are difficult to diagnose and classify by blood and bone marrow examination.As a surface marker of granulocyte,studies have shown CD10 can be used to define the degree of granulocyte maturation in MDS patients.However,whether it can be used for differential diagnosis of MDS and other hematological diseases remains inconclusive.To explore the value of CD10 for differential diagnosis of MDS,60 newly diagnosed MDS,20 aplastic anemia(AA)patients,and 35 iron-deficient anemia(IDA)patients were selected for this study.Bone marrow(BM)specimens were processed for surface marker analysis and labeled with pre-conjugated monoclonal antibodies.Stained cells were detected by flow cytometry.Our results indicated that CD10-positive granulocytes were significantly decreased in BM of MDS patients than AA and IDA patients,and the level of CD10-positive mature granulocytes was not associated with the clinical stages of malignancy.Receiver operating characteristic(ROC)areas under the curve(AUC)of CD10-positive granulocytes was 0.86 and 0.85,respectively,in MDS patients than the IDA group and AA group with good specificity and sensitivity.Further,CD10-positive granulocytes were increased after effective treatment.In conclusion,we found the decrease in CD10-positive granulocytes has a differential diagnostic value of MDS.
文摘Hepatorenal syndrome with acute kidney injury(HRS-AKI)is a form of rapidly progressive kidney dysfunction in patients with decompensated cirrhosis and/or acute severe liver injury such as acute liver failure.Current data suggest that HRS-AKI occurs secondary to circulatory dysfunction characterized by marked splanchnic vasodilation,leading to reduction of effective arterial blood volume and glomerular filtration rate.Thus,volume expansion and splanchnic vasoconstriction constitute the mainstay of medical therapy.However,a significant proportion of patients do not respond to medical management.These patients often require renal replacement therapy and may be eligible for liver or combined liver-kidney transplantation.Although there have been advances in the management of patients with HRS-AKI including novel biomarkers and medications,better-calibrated studies,more widely available biomarkers,and improved prognostic models are sorely needed to further improve diagnosis and treatment of HRS-AKI.
基金This work was supported by The Nature Science Foundation of China(Nos.82070176,82070128,81900132)the Medical Science and Technology Research Fund of Guangdong Province(No.A2020585).
文摘The pathogenesis of myelodysplastic syndrome(MDS)may be related to the abnormal expression of microRNAs(miRNAs),which could influence the differentiation capacity of mesenchymal stem cells(MSCs)towards adipogenic and osteogenic lineages.In this study,exosomes from bone marrow plasma were successfully extracted and identified.Assessment of miR-103-3p expression in exosomes isolated from BM in 34 MDS patients and 10 controls revealed its 0.52-fold downregulation in patients with MDS compared with controls(NOR)and was downregulated 0.55-fold in MDS-MSCs compared with NOR-MSCs.Transfection of MDS-MSCs with the miR-103-3p mimic improved osteogenic differentiation and decreased adipogenic differentiation in vitro,while inhibition of miR-103-3p showed the opposite results in NOR-MSCs.Thus,the expression of miR-103-3p decreases in MDS BM plasma and MDS-MSCs,significantly impacting MDS-MSCs differentiation.The miR-103-3p mimics may boost MDS-MSCs osteogenic differentiation while weakening lipid differentiation,thereby providing possible target for the treatment of MDS pathogenesis.
基金Major Project of Jinhua Science and Technology Bureaun,No.2021-3-025。
文摘BACKGROUND Patients with trisomy 8 consistently present with myeloid neoplasms and/or auto-inflammatory syndrome.A possible link between myelodysplastic syndromes(MDS)with trisomy 8(+8-MDS)and inflammatory disorders is well recognized,several cases having been reported.However,inflammatory disorders in patients without MDS have been largely overlooked.Generally,Behçet's disease is the most common type in+8-MDS.However,inflammatory disorders with pulmonary involvement are less frequent,and no effective treatment has been established.CASE SUMMARY A 27-year-old man with recurrent fever,fatigue for>2 mo,and unconsciousness for 1 day was admitted to our emergency department with a provisional diagnosis of severe pneumonia.Vancomycin and imipenem were administered and sputum collected for metagenomic next-generation sequencing.Epstein–Barr virus and Mycobacterium kansasii were detected.Additionally,chromosomal analysis showed duplications on chromosome 8.Two days later,repeat metagenomic next-generation sequencing was performed with blood culture.Cordyceps portugal,M.kansasii,and Candida portugal were detected,and duplications on chromosome 8 confirmed.Suspecting hematological disease,we aspirated a bone marrow sample from the iliac spine,examination of which showed evidence of infection.We added fluconazole as further antibiotic therapy.Seven days later,the patient’s condition had not improved,prompting addition of methylprednisolone as an anti-inflammatory agent.Fortunately,this treatment was effective and the patient eventually recovered.CONCLUSION Severe inflammatory disorders with pulmonary involvement can occur in patients with trisomy 8.Methylprednisolone may be an effective treatment.
基金Supported by The Specialized Scientific Research Fund Projects of The Medical Group of Qingdao University,No.YLJT20201002.
文摘BACKGROUND Myelodysplastic syndrome(MDS)is a hematological neoplasm,and an increase in myeloblasts is representative of leukemic hematopoiesis in advanced MDS.Lowrisk MDS usually exhibits deranged autoimmunity resembling that of aplastic anemia(AA),whereas advanced MDS is characterized by a phenotype of immune exhaustion.MDS can be normo/hyperplastic or hypoplastic.Generally,bone marrow cellularity and myeloblasts increase with disease progression.Transformation from advanced MDS to AA-like syndrome with leukemic cell regression has not previously been reported.CASE SUMMARY A middle-aged Chinese woman had a 4-year history of leukocytopenia.Six months prior to admission,the patient developed gradually worsening fatigue and performance status.The leukocytopenia further progressed.She was diagnosed with MDS with excess blasts-2 based on increased bone marrow cellularity and an increased percentage of myeloblasts on marrow and blood smears,an increased percentage of cluster of differentiation(CD)34+CD33+progenitors in immunotyping analysis,a normal karyotype in cytogenetic analysis,and the identification of somatic mutations in CBL,KMT2D and NF1 in molecular analysis.Initially,neutropenia was the predominant hematological abnormality,with mild anemia and thrombocytosis,and the degree of fatigue was far more severe than the degree of anemia.In the following months,the patient experienced several febrile episodes.Intravenous antibiotic treatments were able to control the febrile episodes,but the elevated inflammatory indices persisted.The hematological parameters dramatically fluctuated with the waxing and waning of the inflammatory episodes.With recurrent flares of the inflammatory condition,agranulocytosis and severe anemia developed,with mild thrombocytopenia.During the patient’s hospitalization,computed tomography(CT)scans revealed the presence of extensive inflammatory lesions involving the lungs,mediastinum,pleura,gastrointestinal tract,peritoneum and urinary tract,with imaging features suggestive of the reactivation of disseminated tuberculosis.Reevaluation of the bone marrow smears revealed that the cellularity became hypoplastic,and the leukemic cells regressed,suggesting that both normal and leukemic hematopoiesis had been heavily suppressed.Immunological analysis of the bone marrow samples revealed a decreased percentage of CD34+cells and an immunological signature resembling that of severe AA(SAA),confirming the regression of the leukemic cells by autoimmune-mediated attacks.The patient demonstrated resistance to multiple drugs,including antituberculotics,recombinant human granulocyte colony-stimulating factor,broad-spectrum antibiotics,voriconazole,ganciclovir,immune suppressants,eltrombopag and intravenous immunoglobulin,which further worsened the hematological injury and patient’s performance status.The patient eventually died of overwhelming infection and multidrug resistance.CONCLUSION Advanced MDS can transform to aplastic cytopenia with leukemic cell regression and an immunological signature of SAA during inflammatory flare-ups.
基金Supported by The Specialized Scientific Research Fund Projects of The Medical Group of Qingdao University,No.YLJT20201002.
文摘BACKGROUND Myelodysplastic syndrome(MDS)is caused by malignant proliferation and ineffective hematopoiesis.Oncogenic somatic mutations and increased apoptosis,necroptosis and pyroptosis lead to the accumulation of earlier hematopoietic progenitors and impaired productivity of mature blood cells.An increased percentage of myeloblasts and the presence of unfavorable somatic mutations are signs of leukemic hematopoiesis and indicators of entrance into an advanced stage.Bone marrow cellularity and myeloblasts usually increase with disease progression.However,aplastic crisis occasionally occurs in advanced MDS.CASE SUMMARY A 72-year-old male patient was definitively diagnosed with MDS with excess blasts-1(MDS-EB-1)based on an increase in the percentages of myeloblasts and cluster of differentiation(CD)34+hematopoietic progenitors and the identification of myeloid neoplasm-associated somatic mutations in bone marrow samples.The patient was treated with hypomethylation therapy and was able to maintain a steady disease state for 2 years.In the treatment process,the advanced MDS patient experienced an episode of progressive pancytopenia and bone marrow aplasia.During the aplastic crisis,the bone marrow was infiltrated with sparsely distributed atypical lymphocytes.Surprisingly,the leukemic cells disappeared.Immunological analysis revealed that the atypical lymphocytes expressed a high frequency of CD3,CD5,CD8,CD16,CD56 and CD57,suggesting the activation of autoimmune cytotoxic T-lymphocytes and natural killer(NK)/NKT cells that suppressed both normal and leukemic hematopoiesis.Elevated serum levels of inflammatory cytokines,including interleukin(IL)-6,interferon-gamma(IFN-γ)and tumor necrosis factor-alpha(TNF-α),confirmed the deranged type I immune responses.This morphological and immunological signature led to the diagnosis of severe aplastic anemia secondary to large granule lymphocyte leukemia.Disseminated tuberculosis was suspected upon radiological examinations in the search for an inflammatory niche.Antituberculosis treatment led to reversion of the aplastic crisis,disappearance of the atypical lymphocytes,increased marrow cellularity and 2 mo of hematological remission,providing strong evidence that disseminated tuberculosis was responsible for the development of the aplastic crisis,the regression of leukemic cells and the activation of CD56+atypical lymphocytes.Reinstitution of hypomethylation therapy in the following 19 mo allowed the patient to maintain a steady disease state.However,the patient transformed the disease phenotype into acute myeloid leukemia and eventually died of disease progression and an overwhelming infectious episode.CONCLUSION Disseminated tuberculosis can induce CD56+lymphocyte infiltration in the bone marrow and in turn suppress both normal and leukemic hematopoiesis,resulting in the development of aplastic crisis and leukemic cell regression.
文摘BACKGROUND Sotos syndrome is an autosomal dominant disorder,whereas attention-deficit/hyperactivity disorder(ADHD)is a neurodevelopmental condition.This report aimed to summarize the clinical and genetic features of a pediatric case of Soros syndrome and ADHD in a child exhibiting precocious puberty.CASE SUMMARY The patient presented with accelerated growth and advanced skeletal maturation;however,she lacked any distinct facial characteristics related to specific genetic disorders.Genetic analyses revealed a paternally inherited heterozygous synonymous mutation[c.4605C>T(p.Arg1535Arg)].Functional analyses suggested that this mutation may disrupt splicing,and bioinformatics analyses predicted that this mutation was likely pathogenic.After an initial diagnosis of Sotos syndrome,the patient was diagnosed with ADHD during the follow-up period at the age of 8 years and 7 months.CONCLUSION The potential for comorbid ADHD in Sotos syndrome patients should be considered to avoid the risk of a missed diagnosis.
文摘Amniotic band syndrome is an acquired embryo-fetopathy. It is rare and is characterized by malformations mainly affecting the limbs but also the skull, face and thoraco-abdominal axis. Its etiopathogenesis remains poorly understood. Its diagnosis is essentially clinical and is classically based on the existence of signs such as furrows, amputations and pseudosyndactyly. To show the importance of antenatal diagnosis in resource-limited countries, we report the case of two newborns, one premature at 31 weeks and the other at term, in whom amniotic band syndrome was discovered incidentally at birth. It involved an amputation of the right leg for both cases. The premature baby was born in a context of neonatal sepsis and will succumb to the latter while the 2nd case was released from the hospital alive. Imaging examinations to search for probable congenital malformations could only be carried out for the 2nd case and no accessible congenital malformation had been identified. And as management of the disease, only psychological support to the parents was provided for the 2 cases. The antenatal discovery of a case of amniotic band syndrome in countries with low technical capacity such as Burundi should push clinicians to think in time about treatment options.
文摘Introduction: Prostate cancer is one of the most common cancers in men. In cases of suspected locally advanced disease or lymph node or bone metastases, thoraco-abdomino-pelvic CT is still useful for detecting visceral metastases. In the course of this extension work-up, other abnormalities may be discovered by chance, which had previously remained silent, and which could be diagnosed and managed in childhood, hence the interest of presenting a case of incidental finding of pyeloureteral junction syndrome during extension workup for prostatic adenocarcinoma at Yaounde Central Hospital. Observation: A 72-year-old patient presented to the department with acute urinary retention. The clinical examination, with an empty bladder, and in particular the digital rectal exam (DRE), was in favor of malignant prostatic hypertrophy. A workup was ordered, including a total PSA returned to 61.3 ng/ml (PSA performed one week after the episode of acute urinary retention) with cytobacteriological examination of sterile urine. Renal function was slightly impaired, with creatinemia at 14 ng/ml. Renal and vesico-prostatic ultrasound revealed a 57 g prostate with regular, clean contours and a polycystic right kidney. A prostate biopsy was indicated, which revealed a histopathological aspect in favor of a prostatic adenocarcinoma ISUP 1. An extension work-up including a thoraco-abdomino-pelvic CT scan revealed no signs of local or distant secondary localization, but a pyeloureteral junction syndrome with significant hydronephrosis, parenchymal destruction and compensatory hypertrophy of the contralateral kidney was found. Conclusion: The prostate cancer extension work-up revealed a pathology that can be diagnosed early. It is therefore important to reinforce prenatal and natal screening, which will enable malformative uropathies to be identified early and corrected in time to preserve patients’ renal function. Furthermore, we must be careful in the ultrasound diagnosis of pyeloureteral junction syndrome.
文摘Irritable bowel syndrome (IBS) is a chronic and debilitating functional gastrointestinal disorder that affects 9%-23% of the population across the world. The percentage of patients seeking health care related to IBS approaches 12% in primary care practices and is by far the largest subgroup seen in gastroenterology clinics. It has been well documented that these patients exhibit a poorer quality of life and utilize the health care system to a greater degree than patients without this diagnosis. The pathophysiology of IBS is not clear. Many theories have been put forward, but the exact cause of IBS is still uncertain. According to the updated ROME III criteria, IBS is a clinical diagnosis and presents as one of the three predominant subtypes: (1) IBS with constipation (IBS-C); (2) IBS with diarrhea (IBS-D); and (3) mixed IBS (IBS-M); former ROME definitions refer to IBS-M as alternating IBS (IBS-A). Across the IBS subtypes, the presentation of symptoms may vary among patients and change over time. Patients report the most distressing symptoms to be abdominal pain, straining, myalgias, urgency, bloating and feelings of serious illness. The complexity and diversity of IBS presentation makes treatment difficult. Although there are reviews and guidelines for treating IBS, they focus on the efficacy of medications for IBS symptoms using high-priority endpoints, leaving those of lower priority largely unreported. Therefore, the aim of this review is to provide a comprehensive evidence-based review of the diagnosis, pathogenesis and treatment to guide clinicians diagnosing and treating their patients.
文摘Irritable bowel syndrome (IBS) is the most frequently diagnosed functional gastrointestinal disorder in primary and secondary care. It is characterised by abdominal discomfort, pain and changes in bowel habits that can have a serious impact on the patient’s quality of life. The pathophysiology of IBS is not yet completely clear. Genetic, immune, environmental, inflammatory, neurological and psychological factors, in addition to visceral hypersensitivity, can all play an important role, one that most likely involves the complex interactions between the gut and the brain (gut-brain axis). The diagnosis of IBS can only be made on the basis of the symptoms of the Rome III criteria. Because the probability of organic disease in patients fulfilling the IBS criteria is very low, a careful medical history is critical and should pay particular attention to the possible comorbidities. Nevertheless, the severity of the patient’s symptoms or concerns sometimes compels the physician to perform useless and/or expensive diagnostic tests, transforming IBS into a diagnosis of exclusion. The presence of alarming symptoms (fever, weight loss, rectal bleeding, significant changes in blood chemistry), the presence of palpable abdominal masses, any recent onset of symptoms in patient aged over 50 years, the presence of symptoms at night, and a familial history of celiac disease, colorectal cancer and/or inflammatory bowel diseases all warrant investigation. Treatment strategies are based on the nature and severity of the symptoms, the degree of functional impairment of the bowel habits, and the presence of psychosocial disorders. This review examines and discusses the pathophysiological aspects and the diagnostic and therapeutic approaches available for patients with symptoms possibly related to IBS, pointing out controversial issues and the strengths and weaknesses of the current knowledge.
基金Yusuf Bayraktar, MD, Gastroenterology Department, Hacettepe University School of Medicine, Ankara, Turkey. bayrak@hacettepe.edu.trTelephone: +90-312-3051712 Fax: +90-312-3051490
文摘Budd-Chiari syndrome is a congestive hepatopathy caused by blockage of hepatic veins. This syndrome occurs in 1/100 000 in the general population. Hypercoagulable state could be identified in 75% of the patients; more than one etiologic factor may play a role in 25% of the patients. Primary myeloproliferative diseases are the leading cause of the disease. Two of the hepatic veins must be blocked for clinically evident disease. Liver congestion and hypoxic damage of hepatocytes eventually result in predominantly centrilobular fibrosis. Doppler ultrasonography of the liver should be the initial diagnostic procedure. Hepatic venography is the reference procedure if required. Additionally liver biopsy may be helpful for differential diagnosis. The prognosis of the chronic form is acceptable compared to other chronic liver diseases.
文摘Presented in this paper is our experience in the diagnosis and management of abdominal compartment syndrome during severe acute pancreatitis. On the basis of the history of severe acute pancreatitis, after effective fluid resuscitation, if patients developed renal, pulmonary and cardiac insufficiency after abdominal expansion and abdominal wall tension, ACS should be considered. Cystometry could be performed to confirm the diagnosis. Emergency decompressive celiotomy and temporary abdominal closure with a 3 liter sterile plastic bag must be performed. It is also critical to prevent reperfusion syndrome. In 23 cases of ACS, 18 cases received emergency decompressive celiotomy and 5 cases did not. In the former, 3 patients died (16.7 %) while in the later, 4 (80%) died. Total mortality rate was 33.3% (7/21). In 7 death cases, 4 patients developed acute obstructive suppurative cholangitis (AOSC). All the patients who received emergency decompressive celiotomy 5 h after confirmation of ACS survived. The definitive abdominal closure took place mostly 3 to 5 days after emergency decompressive celiotomy, with longest time being 8 days. 6 cases of ACS at infection stage were all attributed to infected necrosis in abdominal cavity and retroperitoneum. ACS could occur in SIRS stage and infection stage during SAP, and has different pathophysiological basis. Early diagnosis, emergency decompressive celiotomy and temporary abdominal closure with a 3L sterile plastic bag are the keys to the management of the condition.
文摘The myelodysplastic/myeloproliferative neoplasms(MDS/MPNs) are a unique group of hematologic malignancies characterized by concomitant myelodysplastic and myeloproliferative features. According to the 2008 WHO classification, the category includes atypical chronic myeloid leukemia(a CML), chronic myelomonocytic leukemia(CMML), juvenile myelomonocytic leukemia(JMML), MDS/MPN-unclassifiable(MDS/MPN-U), and the provisional entity refractory anemia with ring sideroblasts and thrombocytosis(RARS-T). Although diagnosis currently remains based on clinicopathologic features, the incorporation of nextgeneration platforms has allowed for the recent molecular characterization of these diseases which has revealed unique and complex mutational profiles that support their distinct biology and is anticipated to soon play an integral role in diagnosis,prognostication, and treatment. Future goals of research should include the development of disease-modifying therapies, and further genetic understanding of the category will likely form the foundation of these efforts.
基金Supported by Nestle Research International and The Science and Technology Department of Zhejiang Province,No.2009C14016
文摘AIM: To validate 4-sample lactose hydrogen breath testing(4SLHBT) compared to standard 13-sample LHBT in the clinical setting.METHODS: Irritable bowel syndrome patients with diarrhea(IBS-D) and healthy volunteers(HVs) were enrolled and received a 10 g, 20 g, or 40 g doselactose hydrogen breath test(LHBT) in a randomized, double-blinded, controlled trial. The lactase gene promoter region was sequenced. Breath samples and symptoms were acquired at baseline and every 15 min for 3 h(13 measurements). The detection rates of lactose malabsorption(LM) and lactose intolerance(LI) for a 4SLHBT that acquired four measurements at 0, 90, 120, and 180 min from the same data set were compared with the results of standard LHBT.RESULTS: Sixty IBS-D patients and 60 HVs were studied. The genotype in all participants was C/C-13910. LM and LI detection rates increased with lactose dose from 10 g, 20 g to 40 g in both groups(P < 0.001). 4SLHBT showed excellent diagnostic concordance with standard LHBT(97%-100%, Kappa 0.815-0.942) with high sensitivity(90%-100%) and specificity(100%) at all three lactose doses in both groups.CONCLUSION: Reducing the number of measurements from 13 to 4 samples did not significantly impact on the accuracy of LHBT in health and IBS-D. 4SLHBT is a valid test for assessment of LM and LI in clinical practice.
文摘AIM To evaluate factors associated with Clostridium difficile infection (CDI) and outcomes of CDI in the myelodysplastic syndrome(MDS) and acute myeloid leukemia (AML) population.METHODS After IRB approval,all MDS/AML patients hospitalized at the University of Maryland Greenebaum Comprehensive Cancer Center between August 2011 and December 2013 were identified.Medical charts were reviewed for demographics,clinical information,development of CDI,complications of CDI,and mortality.Patients with CDI,defined as having a positive stool PCR done for clinical suspicion of CDI,were compared to those without CDI in order to identify predictors of disease.A t-test was used for comparison of continuous variables and chisquare or Fisher's exact tests were used for categorical variables,as appropriate.RESULTS Two hundred and twenty-three patients (60.1% male,mean age 61.3 years,13% MDS,87% AML) had 594 unique hospitalizations during the study period.Thirtyfour patients (15.2%) were diagnosed with CDI.Factors significantly associated with CDI included lower albumin at time of hospitalization (P < 0.0001),prior diagnosis of CDI (P < 0.0001),receipt of cytarabine-based chemotherapy (P = 0.015),total days of neutropenia (P = 0.014),and total days of hospitalization (P = 0.005).Gender (P = 0.10),age (P = 0.77),proton-pump inhibitor use (P = 0.73),receipt of antibiotics (P = 0.66),and receipt of DNA hypomethylating agent-based chemotherapy (P = 0.92) were not significantly associated with CDI.CONCLUSION CDI is common in the MDS/AML population.Factors significantly associated with CDI in this population include low albumin,prior CDI,use of cytarabine-based chemotherapy,and prolonged neutropenia.In this study,we have identified a subset of patients in which prophylaxis studies could be targeted.
基金supported by grants from NIH(No.1R01LM010185,1U01CA166886,and 1U01HL111560)
文摘Myelodysplastic syndromes have increased in frequency and incidence in the American population, but patient prognosis has not significantly improved over the last decade. Such improvements could be realized if biomarkers for accurate diagnosis and prognostic stratification were successfully identified. In this study, we propose a method that associates two state-of-the-art array technologies-single nucleotide polymorphism (SNP) array and gene expression array-with gene motifs considered transcription factor -binding sites (TFBS). We are particularly interested in SNP-containing motifs introduced by genetic variation and mutation as TFBS. The potential regulation of SNP-containing motifs affects only when certain mutations occur. These motifs can be identified from a group of co-expressed genes with copy number variation. Then, we used a sliding window to identify motif candidates near SNPs on gene sequences. The candidates were filtered by coarse thresholding and fine statistical testing. Using the regression-based LARS-EN algorithm and a level-wise sequence combination procedure, we identified 28 SNP-containing motifs as candidate TFBS. We confirmed 21 of the 28 motifs with ChIP-chip fragments in the TRANSFAC database. Another six motifs were validated by TRANSFAC via searching binding fragments on coregulated genes. The identified motifs and their location genes can be considered potential biomarkers for myelodysplastic syndromes. Thus, our proposed method, a novel strategy for associating two data categories, is capable of integrating information from different sources to identify reliable candidate regulatory SNP-containing motifs introduced by genetic variation and mutation.
