Chronic kidney disease (CKD) and NAFLD: Time for awareness and screening

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Role of the Microbiota and Antibiotics in Primary Sclerosing Cholangitis

Primary sclerosing cholangitis (PSC) is an idiopathic, progressive, cholestatic liver disease with considerable morbidity and mortality and no established pharmacotherapy. In addition to the long-recognized association between PSC and inflammatory bowel disease, several lines of preclinical and clinical evidence implicate the microbiota in the etiopathogenesis of PSC. Here we provide a concise review of these data which, taken together, support further investigation of the role of the microbiota and antibiotics in PSC as potential avenues toward elucidating safe and effective pharmacotherapy for patients afflicted by this illness

The Founder Effect? -FXIII Deficiency in Southeast Iran: A Molecular Study Report

Background: Congenital factor XIII (FXIII) deficiency is an extremely rare bleeding disorder (RBD) with different clinical coagulation disorders and great impacts on the perioperative patient outcome. Its prevalence in Southeast Iran is approximately 4,000 times higher than the worldwide prevalence, with Trp187Arg (c.559T> C as the only causative mutation of FXIIID there. We investigated the founder effect of rs1742924, rs4960181, rs3778360 and rs4142290 using haplotype analysis to define the genetic phenomenon in this geographic region. Materials and Methods: In a case-control study, 10 patients with FXIIID and 10 healthy individuals were assessed. Initially, Trp187Arg (c.559T> C) mutation was assessed in all study populations using a PCR-RFLP technique, then haplotype analysis was performed by assessing rs1742924, rs4960181, rs3778360 and rs4142290 polymorphisms. Data were analyzed using a two-proportion z-test. Results: All patients were homozygote for Trp187Arg (c.559T>C), and this mutation was not observed in any form of homozygote or heterozygote in the control group. Polymorphisms in rs1742924, rs4960181, and rs377836 were homozygote (TT, GG, GG, respectively) and T, G, and G alleles distribution in cases and controls with significant difference (P<0.001, P<0.001, and P=0.01 respectively). Rs4142290 polymorphism showed no significant difference between patients and controls (P=0.3). Two types of haplotypes were observed in the case group, and haplotype number 1* was observed among 90% of them, while not observed in the control group. Conclusion: It seems that founder effectors of haplotype number *1 have more antiquity versus other haplotypes, and probably founder effect is responsible for this high prevalence of FXIIID in the southeast of Iran

Signet Ring Cell Gastric Carcinoma: Clinical Epidemiology and Outcomes in a Predominantly Latino County Hospital Population.

BackgroundGastric signet ring cell carcinoma (GSRC) is a rare but increasingly prevalent tumor histotype whose clinical features and natural history are poorly understood, particularly in the USA and minorities.AimsTo examine the occurrence, clinico-demographic characteristics, oncologic features, treatment, and outcomes of GSRC in a predominantly minority county hospital setting and benchmark them against data from the National Cancer Institute's Surveillance, Epidemiology, and End Results (SEER) program.MethodsWe queried biopsy-proven GSRC cases at a Los Angeles County hospital, from 2004 to 2017. Clinical characteristics, treatment, and survival data were collected and compared to SEER data.ResultsWe identified 63 patients with GSRC. Compared to SEER, our cohort was significantly younger (52.6 vs. 63.5 years, p < 0.01), Hispanic/Latino predominant (81% vs. 20%, p < 0.01), had higher overall stage (86% vs. 69% with stage III/IV, p < 0.01), and more frequent node involvement (89% vs. 49%, p < 0.01). Lower tumor stage, Helicobacter pylori positivity, and surgical intervention were associated with significantly longer median survival (all p < 0.05), which was similar in our study compared to SEER (median 12.6 vs. 9.0 months, p = 0.26).ConclusionsPatients with GSRC within the Los Angeles County population have different clinical characteristics compared to what has been reported in SEER. Our cohort was younger, and despite having more advanced disease, did not have shorter survival. Further study is needed to better identify protective and risk factors in this population and improve understanding of the etiopathogenesis and natural history of this malignancy

Role of the Microbiota and Antibiotics in Primary Sclerosing Cholangitis

Primary sclerosing cholangitis (PSC) is an idiopathic, progressive, cholestatic liver disease with considerable morbidity and mortality and no established pharmacotherapy. In addition to the long-recognized association between PSC and inflammatory bowel disease, several lines of preclinical and clinical evidence implicate the microbiota in the etiopathogenesis of PSC. Here we provide a concise review of these data which, taken together, support further investigation of the role of the microbiota and antibiotics in PSC as potential avenues toward elucidating safe and effective pharmacotherapy for patients afflicted by this illness

A huge intraductal papillary mucinous carcinoma of the bile duct treated by right trisectionectomy with caudate lobectomy

<p>Abstract</p> <p>Background</p> <p>Because intraductal papillary mucinous neoplasm of the bile duct (IPMN-B) is believed to show a better clinical course than non-papillary biliary neoplasms, it is important to make a precise diagnosis and to perform complete surgical resection.</p> <p>Case presentation</p> <p>We herein report a case of malignant IPMN-B treated by right trisectionectomy with caudate lobectomy and extrahepatic bile duct resection. Radiologic images showed marked dilatation of the left medial sectional bile duct (B4) resulting in a bulky cystic mass with multiple internal papillary projections. Duodenal endoscopic examination demonstrated very patulous ampullary orifice with mucin expulsion and endoscopic retrograde cholangiogram confirmed marked cystic dilatation of B4 with luminal filling defects. These findings suggested IPMN-B with malignancy potential. The functional volume of the left lateral section was estimated to be 45%. A planned extensive surgery was successfully performed. The remnant bile ducts were also dilated but had no macroscopic intraluminal tumorous lesion. The histopathological examination yielded the diagnosis of mucin-producing oncocytic intraductal papillary carcinoma of the bile duct with poorly differentiated carcinomas showing neuroendocrine differentiation. The tumor was 14.0 × 13.0 cm-sized and revealed no stromal invasiveness. Resection margins of the proximal bile duct and hepatic parenchyma were free of tumor cell. The patient showed no postoperative complication and was discharged on 10^thpostoperative date. He has been regularly followed at outpatient department with no evidence of recurrence.</p> <p>Conclusion</p> <p>Considering a favorable prognosis of IPMN-B compared to non-papillary biliary neoplasms, this tumor can be a good indication for aggressive surgical resection regardless of its tumor size.</p

Association of non-alcoholic fatty liver disease with chronic kidney disease: a systematic review and meta-analysis.

To access publisher's full text version of this article, please click on the hyperlink in Additional Links field or click on the hyperlink at the top of the page marked Files. This article is open access.Chronic kidney disease (CKD) is a frequent, under-recognized condition and a risk factor for renal failure and cardiovascular disease. Increasing evidence connects non-alcoholic fatty liver disease (NAFLD) to CKD. We conducted a meta-analysis to determine whether the presence and severity of NAFLD are associated with the presence and severity of CKD.English and non-English articles from international online databases from 1980 through January 31, 2014 were searched. Observational studies assessing NAFLD by histology, imaging, or biochemistry and defining CKD as either estimated glomerular filtration rate (eGFR) <60 ml/min/1.73 m2 or proteinuria were included. Two reviewers extracted studies independently and in duplicate. Individual participant data (IPD) were solicited from all selected studies. Studies providing IPD were combined with studies providing only aggregate data with the two-stage method. Main outcomes were pooled using random-effects models. Sensitivity and subgroup analyses were used to explore sources of heterogeneity and the effect of potential confounders. The influences of age, whole-body/abdominal obesity, homeostasis model of insulin resistance (HOMA-IR), and duration of follow-up on effect estimates were assessed by meta-regression. Thirty-three studies (63,902 participants, 16 population-based and 17 hospital-based, 20 cross-sectional, and 13 longitudinal) were included. For 20 studies (61% of included studies, 11 cross-sectional and nine longitudinal, 29,282 participants), we obtained IPD. NAFLD was associated with an increased risk of prevalent (odds ratio [OR] 2.12, 95% CI 1.69-2.66) and incident (hazard ratio [HR] 1.79, 95% CI 1.65-1.95) CKD. Non-alcoholic steatohepatitis (NASH) was associated with a higher prevalence (OR 2.53, 95% CI 1.58-4.05) and incidence (HR 2.12, 95% CI 1.42-3.17) of CKD than simple steatosis. Advanced fibrosis was associated with a higher prevalence (OR 5.20, 95% CI 3.14-8.61) and incidence (HR 3.29, 95% CI 2.30-4.71) of CKD than non-advanced fibrosis. In all analyses, the magnitude and direction of effects remained unaffected by diabetes status, after adjustment for other risk factors, and in other subgroup and meta-regression analyses. In cross-sectional and longitudinal studies, the severity of NAFLD was positively associated with CKD stages. Limitations of analysis are the relatively small size of studies utilizing liver histology and the suboptimal sensitivity of ultrasound and biochemistry for NAFLD detection in population-based studies.The presence and severity of NAFLD are associated with an increased risk and severity of CKD. Please see later in the article for the Editors' Summary.Italian Ministry of University/FIRB/MERIT RBNE08NKH7_00

Gastrointestinal bleeding in a newborn infant with congenital factor X deficiency and COVID-19—A common clinical feature between a rare disorder and a new, common infection

Dear Editors, Congenital factor X (FX) deficiency is an extremely rare, bleeding disorder with an estimated incidence of one per 1 million. Patients with severe FX deficiency (FX:C < 1%) demonstrate a wide spectrum of serious clinical presentations, including hemarthrosis, hematoma, gastrointestinal (GI) bleeding, intracranial hemorrhage (ICH), and umbilical cord bleeding.1 In fact, severe FX deficiency, with a high rate of life‐threatening bleeding, is the second‐most severe, rare coagulation factor deficiency (RCFD) after FXIII deficiency.1, 2 Although homozygotes are at risk of severe bleeding, heterozygotes usually are asymptomatic, but postsurgical bleeding or bleeding after childbirth may occur.1, 2 Other risk factors can increase the risk of bleeding in FX deficiency, and coronavirus disease 2019 (COVID‐19), a new medical challenge, could affect the patient's bleeding or thrombotic tendency.3 COVID‐19, which is caused by severe acute respiratory syndrome coronavirus 2 (SARS‐CoV‐2) presents an enormous challenge for everyone, especially for those with underlying risk factors such as cardiovascular disease, diabetes, obesity, and renal failure. Age and male sex are other risk factors.4 Limited data are available regarding the effect of COVID‐19 on patients with congenital bleeding disorders (CBDs), particularly RCFDs.5 It has been shown that hypercoagulability‐related adverse consequences are less common among patients with CBDs, at least in those with moderate‐to‐severe deficiency, but further studies, including our ongoing work on a large number of patients, are required.5 Although there are several reports of newborns among infected pregnant mothers, this is the first report of such a case in an RCFD. This case report may help medical professionals to better manage similar cases. A 19‐year‐old pregnant woman was infected with SARS‐CoV‐2 early in the 9th month of pregnancy. Reverse transcriptase‐polymerase chain reaction (RT‐PCR) confirmed the infection. The patient had been in close contact with family members with confirmed COVID‐19. The patient had cough and fever. Due to the mild presentation, she was given Azithromycin and advised to isolate herself at home. The symptoms resolved within 14 days. At end of her 9th month, three days prior to the planned cesarean section, she was rechecked for SARS‐CoV‐2 infection; her RT‐PCR was negative. She successfully underwent cesarean section without complications and delivered a healthy full‐term baby. Therefore, mother and newborn discharged the following morning. In the evening, the baby experienced bloody vomiting and was hospitalized for further assessment, which showed GI bleeding. At admission, laboratory tests showed a positive C‐reactive protein (CRP) (qualitative), a low hemoglobin level, and prolonged prothrombin time (PT), and activated partial thromboplastin time (APTT) (Table 1). He was hospitalized in the neonate intensive care unit (NICU) for 10 days. Due to the risk of SARS‐CoV‐2 infection, on the third day after admission he was tested by RT‐PCR, which was positive. The neonate received 30 mL frozen plasma (FFP) six times over 10 days, which resolved the GI bleeding. Tranexamic acid (TXA) was administered at a dose of 10 mg/kg every 8 hours. Due to lack of COVID‐19 symptoms, he did not receive any special treatment for the disorder. After 10‐day hospitalization in the NICU, the neonate was sent to an isolation room for 5 days, during which his condition stabilized, after which he was discharged in stable condition. He has had no complications during the past two months after discharge. Since the child's father and two other first‐degree family members have severe FX deficiency, and the parents of the baby are closely related, the mother and the baby were checked for FX deficiency. Routine coagulation tests, and FX:C assay performed by STA Compact automatic coagulometer (Stago, Paris, France), revealed a severe deficiency in the baby, and a mild deficiency, compatible with heterozygote FX deficiency, in the mother (Table 1). Table 1. Laboratory characteristics of mother and baby with factor X deficiency and COVID‐19 Test Proband (2nd day after birth) Proband (7th day after birth) Proband (2 months after hospital discharge) Mother (about 3 1/2 months after SARS‐CoV‐2 infection) WBC × 109/L 14.2 (8‐24)b 9.43 (5‐21) 10.79 (6‐18) 8.7 (3.6‐10.6) RBC × 109/L 2.5 (4.36‐5.96) 2.78 (4.2‐5.8) 3.50 (3.4‐5) 4.41 (3.8‐5.2) Hb (g/dL) 8.2 (16.4‐20.8) 9.2 (15.2‐20.4) 10.2 (10.6‐16.4) 13.6 (12‐15) HCT (%) 24.6 (48‐68) 27 (50‐64) 29.2 (32‐50) 41.4 (35‐49) Lymphocyte × 109/L 6.4 (1.3‐11) 4.3 (1.2‐11.3) 8.21 (2.5‐13) 2.22 (1‐3.2) Neutrophil × 109/L 4.9 (2.6‐17) 2.9 (1.5‐12.6) 1.85 (1.2‐8.1) 5.75 (1.7‐7.5) Platelet × 109/L 370 (150‐450) 331 (150‐450) 334 (150‐450) 276 (150‐450) PT (sec) >60 (PTC: 12.6) 90 (PTC: 12.6) >60 (PTC: 10) 13 (PTC: 10) APTT (sec) >120 (APTTC: 31) 100 (APTTC: 30) >120 (APTTC: 32) 37 (APTTC: 32) CRP (Quantitative) Trace Negative NC NC FX:C level NC NC <1% (50%‐150%) 40% (50%‐150%) Abbreviations: APTT, activated partial thromboplastin time; APTTC, APTT control; CRP, C‐reactive protein; Hb, hemoglobin; HCT, hematocrit; NC, Not checked; PT, prothrombin time; PTC, PT control; RBC, red blood cell; WBC, white blood cell. a Hematological test normal ranges are extracted from Rodak's Hematology: Clinical Principles and Applications, 5th Ed (2016). b Normal values are placed in parentheses. COVID‐19 is an emerging medical challenge that can present more difficulties for those with special conditions, such as pregnant women and newborns. Due to alterations in cellular immunity, pregnant women are more prone to infection by intracellular pathogens like viruses.6 The fetus is also highly susceptible to infection due to immaturity of the immune system.7 Furthermore, the mother's (heterozygote) congenital coagulopathy and that of her newborn (homozygote) were additional potential risk factors, because a disrupted coagulation system is a prominent feature of SARS‐CoV‐2 infection.8 To date, FX deficiency in a newborn has not been cited anywhere as a special condition requiring close attention in the case of SARS‐CoV‐2 infection. According to the few reports to date, SARS‐CoV‐2 infection is a risk factor for severe maternal morbidity. It is worth noting that most of those mothers were discharged without complications.9 From a clinical aspect, fever was the most common symptom (68%) at the time of admission.9 This was also observed in the affected woman of this study. SARS‐CoV‐2 infection can even affect the type of delivery. A systematic review of these women showed that about 92% of deliveries were by cesarean section, less than 10% being the usual vaginal delivery (7 of 85). Fetal distress was mentioned as the most common indication for cesarean section. Our patient underwent a planned cesarean section, due to her previous history. The delivery itself was uneventful, and a healthy baby was delivered, while among other reported cases, a number of complications have been noted.9 As with most other reports, the infant did not have any symptoms at the time of delivery and was discharged the day after birth.9 In a case series of 10 patients, various first clinical presentations were observed, including shortness of breath (n = 6), fever (n = 2), vomiting (n = 1), and rapid heart rate (n = 1).10 In the case at hand, bloody vomiting was the first clinical presentation. In the same case series, one died due to refractory shock, multiple organ failure (MOF), and disseminated intravascular coagulation (DIC). Another patient with severe presentation was managed by intravenous infusions of gamma globulin, platelets, and plasma, which was suggestive of the effectiveness of gamma globulin in severe cases. The author recommended early use of intravenous gamma globulin for passive immunization.10 GI bleeding in our case was successfully managed by administration of FFP and TXA. In addition to thrombotic complication, bleeding is not infrequent in patients affected by COVID‐19, with GI bleeding seemingly the most common hemorrhagic manifestation among adults. GI bleeding, with a frequency of 40%, was observed among neonates from affected mothers.3 On the other hand, GI bleeding is also a relatively common presentation among severely FX deficient patients.1, 2 In fact, GI bleeding can occur in children with severe FX deficiency within the first months of life. It seems that such patients are prone to experience severe bleeding, such as ICH, later in life, in the absence of an appropriate therapeutic strategy, most likely preventative regular secondary prophylaxis.1, 2 In one study of 102 patients with congenital FX deficiency, GI bleeding has been reported in 12% of symptomatic cases.1 In this case, with GI bleeding being a common presentation of SARS‐CoV‐2 infection and congenital FX deficiency, it cannot definitively be attributed to one or the other. Close monitoring of such cases is necessary to decrease related adverse consequences. Although it seems that COVID‐19 is less severe in adults with CBDs, it is a less‐known issue among children and newborns with CBDs. Further reports and studies could provide clarity. Due to their severe bleeding tendency, close monitoring of patients with severe congenital FX deficiency is mandatory, even without potential SARS‐CoV‐2 infection. And close monitoring of neonates with infected mothers is mandatory to prevent severe consequences. Patients with concomitant infection with SARS‐CoV‐2 require even more rigorous preventative and supportive care. ACKNOWLEDGEMENTS We highly appreciate Daisy Morant's valuable aid in improving the English Language of this manuscript. The study was supported and approved by Shahid Beheshti University of Medical Sciences. CONFLICT OF INTEREST The authors have no competing interests. AUTHOR CONTRIBUTIONS A. Dorgalaleh designed the work, performed laboratory analysis, and wrote the manuscript. F Ghazizadeh, M. Baghaipour, A. Dabbagh, Gh. Bahoush, and N Baghaipour performed clinical studies. Sh. Tabibian, M. Jazebi, N. Baghaipour, M. Bahraini, A. Fazeli, and F. Yousefi performed laboratory analysis. All the authors approved the submission