Successful hematopoietic cell transplantation in Fanconi anemia patients with renal impairment using ultra-reduced doses of cyclophosphamide and fludarabine.

Hematopoietic cell transplantation (HCT) remains until now the only curative modality for hematological manifestations in patients with Fanconi anemia (FA). The doses of alkylating agents used in the conditioning of this patient population before HCT are usually significantly decreased due to the genomic instability of the FA cells. FA patients with renal impairment represent a dilemma because of the need to further modify the conditioning regimen according to the degree of renal impairment to avoid additional toxicity. At our institution, we successfully transplanted three FA patients using an ultra-modified regimen.

Multiparametric Approach for the Assessment of Mechanical Prosthetic Tricuspid Leaflet Function.

BACKGROUND: There is a lack of comprehensive echocardiographic data to allow discrimination of normal versus abnormal mechanical prosthetic tricuspid valve (MPTV) leaflet function. The identification of such parameters is essential to optimize diagnostic and therapeutic measures. METHODS: The authors investigated bileaflet MPTV function by comparing transthoracic echocardiographic data from 21 episodes of leaflet dysfunction due to valve thrombosis in 12 patients with data from 56 individuals with normal MPTV function. All episodes of dysfunction were confirmed by transesophageal echocardiography and/or cine fluoroscopy. Transthoracic echocardiography-derived two-dimensional, color, and spectral Doppler variables, including MPTV peak early diastolic velocity (E velocity), mean gradient, pressure half-time, time-velocity integral (TVI) of the MPTV, ratio of TVIMPTV to TVI of the left ventricular outflow tract (LVOT) and TVI of the right ventricular outflow tract (RVOT), and continuity-derived effective orifice area, were measured in both groups. RESULTS: Most episodes of MPTV dysfunction resulted from simultaneous involvement of both leaflets (57%), with leaflet(s) often immobilized in the open or semiopen position (71%). Transthoracic and transesophageal echocardiography performed similarly in detecting abnormal leaflet motion (90% vs 88%, P = .68), whereas transesophageal echocardiography was better in identifying MPTV thrombosis (31% vs 14%, respectively, P = .01). Color Doppler demonstrated flow propagation abnormalities in 67% of episodes of leaflet dysfunction but not in the control group (P < .0001). Doppler variables associated with MPTV leaflet dysfunction included E velocity > 1.6 m/sec, mean gradient > 5 mm Hg, PHT > 157 msec, TVIMPTV > 42 cm, TVIMPTV/TVILVOT > 2.3, TVIMPTV/TVIRVOT > 3.0, and continuity-derived effective orifice area ≤ 1.1 cm2, with most variables showing high and similar accuracy (area under the curve ≥ 95%). CONCLUSIONS: This study represents the first comprehensive echocardiographic assessment of MPTV leaflet dysfunction that provides parameters and criteria to distinguish normal versus abnormal prosthetic valve function.

Larazotide acetate for treatment of celiac disease: A systematic review and meta-analysis of randomized controlled trials.

PURPOSE: The standard of care for treatment of celiac disease (CD) is a stringent lifetime gluten-free diet (GFD). Larazotide acetate (AT-1001) is an anti-zonulin which functions as a gut permeability regulator for treatment of CD. We endeavored to conduct a systematic review and meta-analysis of all randomized controlled trials (RCTs) which studied the efficacy and safety of AT-1001 in patients with CD. METHODS: We examined four databases from inception to 20-August-2020. We pooled continuous outcomes as mean difference and dichotomous outcomes as risk ratio with 95% confidence interval under the fixed-effects meta-analysis model. RESULTS: Four RCTs met our eligibility criteria, comprising 626 patients (AT-1001, n=465, placebo, n=161). Three and two RCTs reported outcomes of patients undergoing gluten challenge (intake of 2.4-2.7 grams of gluten/day) and GFD, respectively. For change in lactulose-to-mannitol ratio, the endpoint did not significantly differ between AT-1001 and placebo groups, irrespective of the gluten status. Subgroup analysis of patients undergoing gluten challenge showed AT-1001 treatment (compared with placebo) significantly correlated with better symptomatic improvement in the two endpoints of change in total gastrointestinal symptom rating scale (total GSRS) and CD-specific GSRS (CD-GSRS). However, no significant difference was noted among patients undergoing GFD for the abovementioned two efficacy endpoints. Compared with placebo, AT-1001 favorably reduced the adverse event (AE) of gluten-related diarrhea in patients who underwent gluten challenge. Other AEs were comparable between both AT-1001 and placebo groups. CONCLUSIONS: AT-1001 is largely well-endured and seems somehow superior to placebo in alleviating gastrointestinal symptoms among CD patients undergoing gluten challenge. Nevertheless, additional RCTs are warranted to validate these findings.

Use of N-Acetylcysteine in Amphetamine-Induced Acute Liver Failure.

Acute liver failure (ALF) is a serious complication of many drugs. Amongst recreational drugs, cocaine, amphetamines and ecstasy (methylenedioxymethamphetamine) have been known to cause ALF as a complication. However, the true effects and management on the liver of such cases have not been well reported and treatment of such conditions needs prompt action. N-acetylcysteine (NAC) is a known hepatoprotective agent but remains controversial in the use of recreational drug-induced acute liver injury. We present a case of ALF secondary to amphetamine ingestion, with a rapid recovery after administration of intravenous NAC.

Polyethylene glycol versus lactulose in the treatment of hepatic encephalopathy: a systematic review and meta-analysis.

BACKGROUND: Hepatic encephalopathy (HE) is defined as brain dysfunction that occurs because of acute liver failure or liver cirrhosis and is associated with significant morbidity and mortality. Lactulose is the standard of care till this date; however, polyethylene glycol (PEG) has gained the attention of multiple investigators. METHODS: We screened five databases namely PubMed, Scopus, Web of Science, Cochrane Library and Embase from inception to 10 February 2021. Dichotomous and continuous data were analysed using the Mantel-Haenszel and inverse variance methods, respectively, which yielded a meta-analysis comparing PEG versus lactulose in the treatment of HE. RESULTS: Four trials with 229 patients were included. Compared with lactulose, the pooled effect size demonstrated a significantly lower average HE Scoring Algorithm (HESA) Score at 24 hours (Mean difference (MD)=-0.68, 95% CI (-1.05 to -0.31), p<0.001), a higher proportion of patients with reduction of HESA Score by ≥1 grade at 24 hours (risk ratio (RR)=1.40, 95% CI (1.17 to 1.67), p<0.001), a higher proportion of patients with a HESA Score of grade 0 at 24 hours (RR=4.33, 95% CI (2.27 to 8.28), p<0.0010) and a shorter time to resolution of HE group (MD=-1.45, 95% CI (-1.72 to -1.18), p<0.001) in favour of patients treated with PEG. CONCLUSION: PEG leads to a higher drop in the HESA Score and thus leads to a faster resolution of HE compared with lactulose.

Keep an Eye Out for Crohn's Disease: Orbital Myositis as the Initial Sign before Gastrointestinal Manifestations.

Extraintestinal manifestations of Crohn's disease sometimes occur and can present prior to intestinal symptoms. Ocular manifestations of Crohn's disease are considered rare, with orbital myositis an even rarer manifestation with only a handful of cases reported in the literature. We present the case of a young woman who was diagnosed with orbital myositis, which was initially attributed to pseudotumor cerebri after an extensive negative work-up. Months later, the patient presented with haematochezia, and was subsequently diagnosed with Crohn's disease. LEARNING POINTS: Orbital myositis is a rare manifestation of inflammatory bowel disease (IBD), and even more rarely is the initial presentation before the development of intestinal luminal disease.Orbital myositis is a rare extraintestinal manifestation of Crohn's disease and mimics thyroid ophthalmopathy. When a thyroid function test is negative, it is important to keep IBD in mind.

A Case of A Mesenteric Cyst Mimicking a Biloma.

Mesenteric cysts are a rare entity, with approximately 1,000 cases reported in the literature. Its etiology is unknown but was theorized to be a benign ectopic lymphatic proliferation in the mesentery. Imaging with surgical excision and pathologic microscopic evaluation is needed for diagnosis, but no specific guidelines for its management have been documented. Per most cases in the literature, drainage of mesenteric cysts is suboptimal and associated with increased risk of recurrence and infection, making surgical resection the treatment of choice. With its varying locations and presentations, diagnosis can be tricky especially given the rarity of its occurrence. Differential diagnosis includes pancreatic pseudocyst, hemangioma, choledochal cyst, hydatid cyst, cystic teratoma, etc. We present a 35-year-old woman who came in with worsening right upper quadrant (RUQ) pain due to chronic cholelithiasis and was found to have a large RUQ cystic mass adherent to the gallbladder, suggesting possible biloma or pancreatic pseudocyst; however, tissue analysis was positive for a mesenteric cyst.