Induction of immune tolerance in patients with hemophilia A and inhibitors treated with porcine VIIIC by home therapy

Home therapy with porcine factor VIIIC was safe and effective when administered to five hemophilic patients over periods of 8 1/2, 6, 4, 3 1/2, and 2 years. No significant transfusion reactions occurred. Before treatment with porcine factor VIIIC, all five had high-level, high- responding anti-human VIIIC inhibitors initially lacking anti-porcine factor VIIIC activity. Although specific anti-porcine VIIIC inhibitors arose in all patients, these were generally transient, and only one patient became refractory to treatment. We believe that porcine factor VIIIC is the treatment of choice in patients whose inhibitors do not cross-react. All five patients lost their original anti-human VIIIC inhibitors after starting treatment with porcine VIIIC, permitting the reintroduction of human VIIIC in three of them. There has been no recurrence of anti-human VIIIC inhibitor activity during 2 to 3 years of regular treatment with human VIIIC in these patients. This suggests that tolerance to human VIIIC has arisen as a result of treatment with porcine VIIIC. Porcine VIIIC may have a role in the desensitization of some factor VIIIC inhibitor patients.     

Locus assignment of two alpha-globin structural mutants from the Caribbean basin: alpha Fort de France (alpha 45 Arg) and alpha Spanish Town (alpha 27 Val)

Two alpha-globin structural mutants were mapped to their encoding loci by in vitro translation of hybrid-selected alpha 1- and alpha 2-globin mRNA. The more highly expressed mutant, alpha Spanish Town (alpha 27Val), is encoded at the alpha 2 locus and the less expressed mutant, alpha Fort de France (alpha 45Arg), is encoded at the alpha 1 locus. These results further define the distribution of alpha-globin structural mutations within the alpha-globin gene cluster and substantiate the dominant role of the alpha 2-globin locus in alpha- globin expression.     

Seroprevalence of hepatitis B and C viruses in moderate and severe COVID-19 inpatients: A cross-sectional study at a referral center in Mexico

Introduction and ObjectivesThe emergence of SARS-CoV-2, which causes the coronavirus disease (COVID-19) has caused a great impact on healthcare systems worldwide, including hepatitis B and C viruses screening and elimination programs. The high number of COVID-19 hospitalizations represent a great opportunity to screen patients for hepatitis B virus (HBV) and hepatitis C virus (HCV), which was the aim of this study.Material and MethodsCross-sectional, retrospective study performed between April 2020 and 20201 at a referral center in Mexico dedicated to the care of adults with severe/critical COVID-19. We retrieved clinical, demographic, and laboratory results from each patient´s medical records, including antibodies against HCV (anti-HCV), HBV surface antigen (HBsAg), antibodies against the HBV core antigen (anti-HBcAg), and antibodies against HBsAg (anti-HBsAg).ResultsOut of 3620 patients that were admitted to the hospital, 24 (0.66%), 4 (0.11%), and 72 (1.99%) tested positive for anti-HCV, HBsAg, and anti-HBcAg, respectively. Of all seronegative patients, 954 (27%) had undetectable anti-HBsAg and 401 (12%) had anti-HBsAg at protective levels. Blood transfusion was the most relevant risk factor. Only 9.7% of the anti-HBc positive, 25% of the HBsAg positive, and 52% of the anti-HCV positive were aware of their serological status.ConclusionsIn this study we found a prevalence of anti-HCV of 0.66%, HBsAg in 0.11%, and isolated anti-HBcAg in 1.99%. We also found that HBV vaccination coverage has been suboptimal and needs to be reinforced. This study gave us a trustworthy insight of the actual seroprevalence in Mexico, which can help provide feedback to the Hepatitis National Elimination Plan.     

Effectiveness of disease management programs in depression: a systematic review

OBJECTIVE: The authors systematically evaluated the published evidence to assess the effectiveness of disease management programs in depression. METHOD: English-language articles on depression were identified through a MEDLINE search for the period from January 1987 to June 2001. Two reviewers evaluated 16,952 published titles, identified 24 depression disease management programs that met explicit inclusion criteria, and extracted data on study characteristics, interventions used, and outcome measures. Pooled effect sizes were calculated by using a random-effects model. RESULTS: Pooled results for disease management program effects on symptoms of depression showed statistically significant improvements (effect size=0.33, N=24). Programs also had statistically significant effects on patients' satisfaction with treatment (effect size=0.51, N=6), patients' compliance with the recommended treatment regimen (effect size=0.36, N=7), and adequacy of prescribed treatment (effect size=0.44, N=11). One program with an explicit screening component showed significant improvement in the rate of detection of depression by primary care physicians (effect size=0.66); two other programs lacking a screening component showed small nonsignificant improvements in the detection rate (effect size=0.18). Disease management programs increased health care utilization (effect size=-0.10, N=8), treatment costs (effect size=-1.03, N=3), and hospitalization (effect size=-0.20, N=2). CONCLUSIONS: Disease management appears to improve the detection and care of patients with depression. Further research is needed to assess the cost-effectiveness of disease management in depression, and consideration should be given to more widespread implementation of these programs.     

Morbid obesity treated by gastroplasty: radionuclide gastric emptying studies

Mechanisms by which gastroplasty for morbid obesity causes weight loss are poorly understood. We studied the role of altered gastric emptying in 50 patients before surgery, 1-4 weeks after surgery, and 2-24 months after surgery using technetium-99m pentetate in water for liquid meals and a Tc-99m styrene divinylbenzene copolymer resin in oatmeal for semisolid meals. We determined the emptying half-times of the stomach before and after surgery in the proximal and distal compartments. The proximal compartment emptied promptly in the early and late postoperative periods. The distal compartment emptied liquids at rates similar to those before surgery, while the late postoperative emptying of semisolids was significantly faster. The stoma connecting the two compartments thus permits rapid transit of liquids and semisolids without delay of distal compartment emptying. No correlation was seen between the emptying half-times or changes thereof and eventual weight loss. Delayed gastric emptying is therefore not the mechanism for satiety and weight loss after gastroplasty has been performed.     

Patients with mutations in NPHS2 (podocin) do not respond to standard steroid treatment of nephrotic syndrome

Nephrotic syndrome (NS) represents the association of proteinuria, hypoalbuminemia, edema, and hyperlipidemia. Steroid-resistant NS (SRNS) is defined by primary resistance to standard steroid therapy. It remains one of the most intractable causes of ESRD in the first two decades of life. Mutations in the NPHS2 gene represent a frequent cause of SRNS, occurring in approximately 20 to 30% of sporadic cases of SRNS. On the basis of a very small number of patients, it was suspected that children with homozygous or compound heterozygous mutations in NPHS2 might exhibit primary steroid resistance and a decreased risk of FSGS recurrence after kidney transplantation. To test this hypothesis, NPHS2 mutational analysis was performed with direct sequencing for 190 patients with SRNS from 165 different families and, as a control sample, 124 patients with steroid-sensitive NS from 120 families. Homozygous or compound heterozygous mutations in NPHS2 were detected for 43 of 165 SRNS families (26%). Conversely, no homozygous or compound heterozygous mutations in NPHS2 were observed for the 120 steroid-sensitive NS families. Recurrence of FSGS in a renal transplant was noted for seven of 20 patients with SRNS (35%) without NPHS2 mutations, whereas it occurred for only two of 24 patients with SRNS (8%) with homozygous or compound heterozygous mutations in NPHS2. None of 29 patients with homozygous or compound heterozygous mutations in NPHS2 who were treated with cyclosporine A or cyclophosphamide demonstrated complete remission of NS. It was concluded that patients with SRNS with homozygous or compound heterozygous mutations in NPHS2 do not respond to standard steroid treatment and have a reduced risk for recurrence of FSGS in a renal transplant. Because these findings might affect the treatment plan for childhood SRNS, it might be advisable to perform mutational analysis of NPHS2, if the patient consents, in parallel with the start of the first course of standard steroid therapy.     

Primary utilization of stents in angioplasty of superficial femoral artery

Percutaneous transluminal angioplasty (PTA) of infrainguinal arteries has been frequently reported in the literature. Independent of the technical feasibility, the results, in short-and long-term follow-up differ among published series. The objective of this article was to assess the long-term results of angioplasty in small, (<3 cm) segmental lesions of the superficial femoral artery treated with primary stenting. Eighteen patients (12 men, 6 women) with lesions of the superficial femoral artery smaller than 3 cm were selected for endovascular treatment and follow-up. The median patient age was 65 years (range, 54 to 84). The indication for treatment was intermittent claudication in 7 patients and critical ischemia (ischemic pain associated with trophic lesions) in 11 patients (62%). Of these, 13 lesions were stenoses and 5 total occlusions. The run-off was good in 15 patients who had more than 2 distal arteries and 3 had only 1 patent artery. During follow-up, all patients were observed with physical examination, progressive exercise treadmill test; pulse volume was measured with Doppler and duplex scan after 1, 3, and 6 months, and then twice a year. There was only 1 primary failure; the initial success rate was 94%. During follow-up of 40 months (6 to 70 months), only 1 patient presented with thrombosis of the stent 6 months after the procedure. There was no symptomatic restenosis in our study. One patient suffered an acute myocardial infraction after 45 months and died. The primary patency after 1 and 3 years was 88%. No patient was lost to follow-up. Primary stenting of segmental lesions (less than 3 cm) of the superficial femoral artery produced satisfactory results immediately and during long-term follow-up.