Publications by authors named "Robert Fisch"

9 Publications

  • Page 1 of 1

The management of clenched fist injuries with local anaesthesia and field sterility.

J Hand Surg Eur Vol 2020 Sep 29:1753193420960588. Epub 2020 Sep 29.

Department of Orthopaedic Surgery, University of Southern California, Los Angeles, CA, USA.

Clenched fist injury is associated with a high risk of infectious complications and is commonly managed with formal irrigation and debridement in the operating theatre. The purpose of this study was to determine outcomes associated with irrigation and debridement of clenched fist injuries under local anaesthesia using field sterility outside the operative theatre. In this single centre study, 232 patients were identified with clenched fist injury and 210 were treated with a standard protocol beginning with administration of intravenous antibiotics and then irrigation and debridement at the bedside. Primary outcome measures were the need for repeat debridement and complications. Secondary outcome measures included factors associated with the need for repeat debridement. Fifteen of the 210 patients (7%) required repeat debridement. Patients with cultures positive for gram-negative organisms had a significantly increased risk of repeat debridement. Irrigation and debridement under local anaesthesia using field sterility results in an acceptably low risk of complications or need for repeat debridement. IV.
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http://dx.doi.org/10.1177/1753193420960588DOI Listing
September 2020

Fatal Cytomegalovirus Infection in an Adult with Inherited NOS2 Deficiency.

N Engl J Med 2020 01;382(5):437-445

From St. Giles Laboratory of Human Genetics of Infectious Diseases, Rockefeller Branch, Rockefeller University (S.B.D., D.H., N.H., S.B., F.R., B.B., R.F., E.J., J.B., L.A., S.B.-D., J.-L.C.), the Department of Microbiology and Immunology, Weill Cornell Medicine (R.B., C.N.), and Howard Hughes Medical Institute (J.-L.C.) - all in New York; the Pediatric Respiratory Diseases Research Center (D.M., S.A.M.), the Department of Clinical Immunology and Infectious Diseases (D.M., N. Mansouri), and the Clinical Tuberculosis and Epidemiology Research Center (D.M., M.M.), National Research Institute of Tuberculosis and Lung Diseases, Shahid Beheshti University of Medical Sciences, Tehran, Iran; the Laboratory of Human Genetics of Infectious Diseases, Necker Branch, INSERM Unité 1163 (A.-L.N., L.L.-D., E.J., J.B., L.A., S.B.-D., V.B., J.-L.C.), Paris University, Imagine Institute (A.-L.N., L.L.-D., E.J., J.B., L.A., S.B.-D., V.B., J.-L.C.), and the Study Center for Primary Immunodeficiencies, Assistance Publique-Hôpitaux de Paris (AP-HP) (J.B.), and the Pediatric Immunology-Hematology Unit (J.-L.C.), Necker Hospital for Sick Children, Paris, and the Department of Pathology, Ambroise Paré Hospital, AP-HP, Boulogne-Billancourt (J.-F.E.) - all in France; the Institute of Experimental Hematology, Hannover Medical School, Hannover, Germany (A.-L.N.); the Research Branch, Sidra Medicine (M.R., T.K., F.A.A., N. Marr), and the College of Health and Life Sciences, Hamad Bin Khalifa University (N. Marr), Doha, Qatar; and the Division of Pulmonary Medicine, Centre Hospitalier Universitaire Vaudois, Lausanne, Switzerland (N. Mansouri).

Background: Cytomegalovirus (CMV) can cause severe disease in children and adults with a variety of inherited or acquired T-cell immunodeficiencies, who are prone to multiple infections. It can also rarely cause disease in otherwise healthy persons. The pathogenesis of idiopathic CMV disease is unknown. Inbred mice that lack the gene encoding nitric oxide synthase 2 () are susceptible to the related murine CMV infection.

Methods: We studied a previously healthy 51-year-old man from Iran who after acute CMV infection had an onset of progressive CMV disease that led to his death 29 months later. We hypothesized that the patient may have had a novel type of inborn error of immunity. Thus, we performed whole-exome sequencing and tested candidate mutant alleles experimentally.

Results: We found a homozygous frameshift mutation in encoding a truncated NOS2 protein that did not produce nitric oxide, which determined that the patient had autosomal recessive NOS2 deficiency. Moreover, all variants that we found in homozygosity in public databases encoded functional proteins, as did all other variants with an allele frequency greater than 0.001.

Conclusions: These findings suggest that inherited NOS2 deficiency was clinically silent in this patient until lethal infection with CMV. Moreover, NOS2 appeared to be redundant for control of other pathogens in this patient. (Funded by the National Center for Advancing Translational Sciences and others.).
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http://dx.doi.org/10.1056/NEJMoa1910640DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7063989PMC
January 2020

Effectiveness of extensor carpi ulnaris tendon lengthening in treating four patients with tendinopathy.

J Hand Surg Eur Vol 2020 01 18;45(1):88-90. Epub 2019 Sep 18.

Department of Orthopaedic Surgery, University of California at Los Angeles, Los Angeles, CA, USA.

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http://dx.doi.org/10.1177/1753193419871521DOI Listing
January 2020

Wrist-Spanning Fixation of Radiocarpal Dislocation: A Cadaveric Assessment of Ulnar Translation.

Hand (N Y) 2019 Sep 13:1558944719873148. Epub 2019 Sep 13.

Keck Medical Center of University of Southern California, Los Angeles, USA.

Radiocarpal dislocations represent a high-energy wrist injury that can occur with or without concomitant fractures about the wrist. Poor outcomes are often due to radiocarpal instability and secondary ulnar translation. The purpose of this cadaveric study is to determine if there is any difference in the radiographic parameters in a wrist dislocation model given the different location of distal fixation. Ten paired fresh cadaver upper extremities were fluoroscopically evaluated with posterior-anterior (PA) and lateral views. We created a radiocarpal dislocation model and applied a dorsal bridge plate to either the second or third metacarpal. Repeat PA and lateral fluoroscopic views were obtained for evaluation of radial inclination, radial height, volar tilt, ulnar variance, radiolunate angle, radioscaphoid angle, scapholunate angle, radial rotation index, and four indices for ulnar translation (Taleisnik, Gilula, McMurtry, and Chamay). Bridge plate application to the second metacarpal resulted in a significantly greater incidence of ulnar translation compared to the third metacarpal. Application to either metacarpal resulted in extension of the carpus relative to the radius. A more anatomic radiocarpal relationship was restored more often when distal fixation of the dorsal wrist-spanning bridge plate was applied to the third metacarpal. Further investigation is warranted to determine clinical relevance of these findings in conjunction with clinical and radiographic outcomes.
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http://dx.doi.org/10.1177/1558944719873148DOI Listing
September 2019

Tuberculosis and impaired IL-23-dependent IFN-γ immunity in humans homozygous for a common missense variant.

Sci Immunol 2018 12;3(30)

St. Giles Laboratory of Human Genetics of Infectious Diseases, Rockefeller Branch, Rockefeller University, New York, NY, USA.

Inherited IL-12Rβ1 and TYK2 deficiencies impair both IL-12- and IL-23-dependent IFN-γ immunity and are rare monogenic causes of tuberculosis, each found in less than 1/600,000 individuals. We show that homozygosity for the common P1104A allele, which is found in about 1/600 Europeans and between 1/1000 and 1/10,000 individuals in regions other than East Asia, is more frequent in a cohort of patients with tuberculosis from endemic areas than in ethnicity-adjusted controls ( = 8.37 × 10; odds ratio, 89.31; 95% CI, 14.7 to 1725). Moreover, the frequency of P1104A in Europeans has decreased, from about 9% to 4.2%, over the past 4000 years, consistent with purging of this variant by endemic tuberculosis. Surprisingly, we also show that TYK2 P1104A impairs cellular responses to IL-23, but not to IFN-α, IL-10, or even IL-12, which, like IL-23, induces IFN-γ via activation of TYK2 and JAK2. Moreover, TYK2 P1104A is properly docked on cytokine receptors and can be phosphorylated by the proximal JAK, but lacks catalytic activity. Last, we show that the catalytic activity of TYK2 is essential for IL-23, but not IL-12, responses in cells expressing wild-type JAK2. In contrast, the catalytic activity of JAK2 is redundant for both IL-12 and IL-23 responses, because the catalytically inactive P1057A JAK2, which is also docked and phosphorylated, rescues signaling in cells expressing wild-type TYK2. In conclusion, homozygosity for the catalytically inactive P1104A missense variant of selectively disrupts the induction of IFN-γ by IL-23 and is a common monogenic etiology of tuberculosis.
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http://dx.doi.org/10.1126/sciimmunol.aau8714DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6341984PMC
December 2018

FFA2 Contribution to Gestational Glucose Tolerance Is Not Disrupted by Antibiotics.

PLoS One 2016 13;11(12):e0167837. Epub 2016 Dec 13.

Division of Endocrinology, Metabolism and Molecular Medicine, Northwestern University Feinberg School of Medicine, Chicago, Illinois, United States of America.

During the insulin resistant phase of pregnancy, the mRNA expression of free fatty acid 2 receptor (Ffar2) is upregulated and as we recently reported, this receptor contributes to insulin secretion and pancreatic beta cell mass expansion in order to maintain normal glucose homeostasis during pregnancy. As impaired gestational glucose levels can affect metabolic health of offspring, we aimed to explore the role of maternal Ffar2 expression during pregnancy on the metabolic health of offspring and also the effects of antibiotics, which have been shown to disrupt gut microbiota fermentative activity (the source of the FFA2 ligands) on gestational glucose homeostasis. We found that maternal Ffar2 expression and impaired glucose tolerance during pregnancy had no effect on the growth rates, ad lib glucose and glucose tolerance in the offspring between 3 and 6 weeks of age. To disrupt short chain fatty acid production, we chronically treated WT mice and Ffar2-/- mice with broad range antibiotics and further compared their glucose tolerance prior to pregnancy and at gestational day 15, and also quantified cecum and plasma SCFAs. We found that during pregnancy antibiotic treatment reduced the levels of SCFAs in the cecum of the mice, but resulted in elevated levels of plasma SCFAs and altered concentrations of individual SCFAs. Along with these changes, gestational glucose tolerance in WT mice, but not Ffar2-/- mice improved while on antibiotics. Additional data showed that gestational glucose tolerance worsened in Ffar2-/- mice during a second pregnancy. Together, these results indicate that antibiotic treatment alone is inadequate to deplete plasma SCFA concentrations, and that modulation of gut microbiota by antibiotics does not disrupt the contribution of FFA2 to gestational glucose tolerance.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0167837PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5154512PMC
June 2017

Normal infant by a gestational carrier for a phenylketonuria mother: alternative therapy.

Mol Genet Metab 2004 May;82(1):83-6

Department of Pediatrics, University of Minnesota, Minneapolis, MN 55455, USA.

The consequences of pregnancies in untreated phenylketonuria (PKU) mothers are a high incidence of spontaneous abortion, intrauterine growth retardation with microcephaly, congenital malformations, and abnormal intellectual development. PKU fathers, on the other hand, produce normal children. Obviously children of PKU women and men are at least heterozygous, proving that the abnormalities produced by the PKU mothers are not genetic but "intrauterinely environmental." Exposure to the mother's metabolic abnormalities affects the fetus during the entire pregnancy. A PKU mother can produce a healthy infant if she maintains a very restricted and controlled diet before and during pregnancy. However, even the most recent reports describe a very high incidence of congenitally abnormal children of PKU mothers, hence dietary compliance is not working in all cases. A 26-year-old PKU patient with proven fertility underwent standard ovarian stimulation in preparation for oocyte retrieval. Following conventional co-incubation of the oocytes and her husband's sperm, two embryos were transferred to the gestational carrier's uterine cavity, resulting in a single intrauterine pregnancy. Birth was induced at 39 weeks of gestation. The male infant weighed 3486 g. Head circumference was 36 cm and length 50.5 cm; there was no evidence of any abnormality and/or malformation. At 1 year of age, the child's growth measurements and development assessments were normal. This describes the first reported successful term pregnancy of an untreated PKU mother with the help of a gestational carrier (GC), producing a normal infant. This is an alternative method that should be offered to PKU women who are unable and/or unwilling to maintain a well controlled diet before and during pregnancy.
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http://dx.doi.org/10.1016/j.ymgme.2004.02.005DOI Listing
May 2004

Books and babies: clinical-based literacy programs.

J Pediatr Health Care 2003 Nov-Dec;17(6):295-300

HealthPartners Research Foundation, Minneapolis, Minn 55440-1524, USA.

Introduction: The purpose of this study was to assess parental response to a clinic-based literacy program at a health maintenance organization. It was hypothesized that participation would be associated with increased literacy orientation by children.

Method: This randomized community trial took place at a Midwestern health maintenance organization. Six clinics were paired and randomly assigned to participate or not participate in Project Read. The main outcome variable was literacy orientation (book use). The target population was parents of children younger than 12 months (N = 165). After 6 months of participation, parents were surveyed by telephone.

Results: Seventy-five percent and 77% of the treatment and control groups, respectively, had positive literacy orientation; this difference was not significant. Persons receiving a videotape were more likely to have a positive literacy orientation (82.9% vs 69.2%; P <.05). The multivariate regression analyses also showed that receiving the free videotape was a significant intervention exposure.

Discussion: The members of the population in this study are reading to their children. Parents who receive a videotape on the importance of reading are likely to read more to their children.
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http://dx.doi.org/10.1016/s0891-5245(03)00071-3DOI Listing
January 2004

Not my fault--call a lawyer.

Authors:
Robert O Fisch

Minn Med 2002 Feb;85(2)

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February 2002