Citations

Extraocular muscle (EOM) entrapment with resulting reduction in motility and diplopia is a known complication of orbital fractures. Less commonly, transection of the EOMs due to trauma, iatrogenic injury, or intentional myotomy may lead to persistent diplopia. The inferior oblique (IO) is often encountered during orbital surgery along the medial wall and floor, and may be disinserted to aid in visualization. The authors present a case of IO entrapment which occurred during zygomaticomaxillary fracture reduction. Intraoperatively, an IO transection was performed and the muscle was reattached within the orbit. Postoperatively, the patient did not develop diplopia or motility disruption. This technique may provide a useful solution to an unusual problem during orbital fracture repair.

Background: Long QT syndrome (LQTS) is a rare genetic disorder and a major preventable cause of sudden cardiac death in the young. A causal rare genetic variant with large effect size is identified in up to 80% of probands (genotype positive) and cascade family screening shows incomplete penetrance of genetic variants. Furthermore, a proportion of cases meeting diagnostic criteria for LQTS remain genetically elusive despite genetic testing of established genes (genotype negative). These observations raise the possibility that common genetic variants with small effect size contribute to the clinical picture of LQTS. This study aimed to characterize and quantify the contribution of common genetic variation to LQTS disease susceptibility. Methods: We conducted genome-wide association studies followed by transethnic meta-analysis in 1656 unrelated patients with LQTS of European or Japanese ancestry and 9890 controls to identify susceptibility single nucleotide polymorphisms. We estimated the common variant heritability of LQTS and tested the genetic correlation between LQTS susceptibility and other cardiac traits. Furthermore, we tested the aggregate effect of the 68 single nucleotide polymorphisms previously associated with the QT-interval in the general population using a polygenic risk score. Results: Genome-wide association analysis identified 3 loci associated with LQTS at genome-wide statistical significance ( P <5×10 −8 ) near NOS1AP , KCNQ1 , and KLF12 , and 1 missense variant in KCNE1 (p.Asp85Asn) at the suggestive threshold ( P <10 −6 ). Heritability analyses showed that ≈15% of variance in overall LQTS susceptibility was attributable to common genetic variation ( h2SNP 0.148; standard error 0.019). LQTS susceptibility showed a strong genome-wide genetic correlation with the QT-interval in the general population (r g =0.40; P =3.2×10 −3 ). The polygenic risk score comprising common variants previously associated with the QT-interval in the general population was greater in LQTS cases compared with controls ( P <10−13), and it is notable that, among patients with LQTS, this polygenic risk score was greater in patients who were genotype negative compared with those who were genotype positive ( P <0.005). Conclusions: This work establishes an important role for common genetic variation in susceptibility to LQTS. We demonstrate overlap between genetic control of the QT-interval in the general population and genetic factors contributing to LQTS susceptibility. Using polygenic risk score analyses aggregating common genetic variants that modulate the QT-interval in the general population, we provide evidence for a polygenic architecture in genotype negative LQTS.

Although peritoneal dialysis (PD)-associated peritonitis secondary to mycobacterium is rare, the treatment is challenging and outcomes remain poor. We report the first case of PD-associated peritonitis secondary to Mycobacterium septicum. The patient is a 53-year-old Caucasian man who developed end-stage kidney disease due to systemic sclerosis. He was initially started on intermittent hemodialysis and was then switched to PD 10 months later. He presented with generalized abdominal pain and an increase in the number of nucleated cells and neutrophils in the dialysate effluent sample (854 total nucleated cells/µL and 512 neutrophils/µL). Ten days later, the fluid grew M. septicum, a rapidly growing nontuberculous mycobacterium (NTM). Once the organism was identified, he was treated with moxifloxacin and doxycycline, and the PD catheter was removed. Antibiotics were adjusted due to sensitivities profile and side effects, and he completed 4 months of antibiotic treatment with decreasing cell counts and negative PD fluid cultures. This case highlights the growing list of organisms responsible for NTM peritonitis and complexity of care in the patient with NTM peritonitis.

Abstract Context Appropriate management of adrenal insufficiency (AI) in pregnancy can be challenging due to the rarity of the disease and lack of evidence-based recommendations to guide glucocorticoid and mineralocorticoid dosage adjustment. Objective Multicenter survey on current clinical approaches in managing AI during pregnancy. Design Retrospective anonymized data collection from 19 international centers from 2013 to 2019. Setting and Patients 128 pregnancies in 113 women with different causes of AI: Addison disease (44%), secondary AI (25%), congenital adrenal hyperplasia (25%), and acquired AI due to bilateral adrenalectomy (6%). Results Hydrocortisone (HC) was the most commonly used glucocorticoid in 83% (97/117) of pregnancies. Glucocorticoid dosage was increased at any time during pregnancy in 73/128 (57%) of cases. In these cases, the difference in the daily dose of HC equivalent between baseline and the third trimester was 8.6 ± 5.4 (range 1-30) mg. Fludrocortisone dosage was increased in fewer cases (7/54 during the first trimester, 9/64 during the second trimester, and 9/62 cases during the third trimester). Overall, an adrenal crisis was reported in 9/128 (7%) pregnancies. Cesarean section was the most frequent mode of delivery at 58% (69/118). Fetal complications were reported in 3/120 (3%) and minor maternal complications in 15/120 (13%) pregnancies without fatal outcomes. Conclusions This survey confirms good maternal and fetal outcome in women with AI managed in specialized endocrine centers. An emphasis on careful endocrine follow-up and repeated patient education is likely to have reduced the risk of adrenal crisis and resulted in positive outcomes.

AbstractUBE2A deficiency, that is, intellectual disability (ID) Nascimento type (MIM 300860), is an X‐linked syndrome characterized by developmental delay, moderate to severe ID, seizures, dysmorphisms, skin anomalies, and urogenital malformations. Forty affected subjects have been reported thus far, with 31 cases having intragenic UBE2A variants. Here, we report on additional eight affected subjects from seven unrelated families who were found to be hemizygous for previously unreported UBE2A missense variants (p.Glu62Lys, p.Arg95Cys, p.Thr99Ala, and p.Arg135Trp) or small in‐frame deletions (p.Val81_Ala83del, and p.Asp101del). A wide phenotypic spectrum was documented in these subjects, ranging from moderate ID associated with mild dysmorphisms to severe features including congenital heart defects (CHD), severe cognitive impairment, and pineal gland tumors. Four variants affected residues (Glu62, Arg95, Thr99 and Asp101) that contribute to stabilizing the structure of the E3 binding domain. The three‐residue in‐frame deletion, p.Val81_Ala83del, resulted from aberrant processing of the transcript. This variant and p.Arg135Trp mapped to regions of the protein located far from the E3 binding region, and caused variably accelerated protein degradation. By reviewing available clinical information, we revise the clinical and molecular profile of the disorder and document genotype‐phenotype correlations. Pineal gland cysts/tumors, CHD and hypogammaglobulinemia emerge as recurrent features.

The need for multiple transducer positions, especially from right parasternal windows, is consistently mentioned in the recommendations for the accurate measurement of peak velocities across a stenotic aortic valve, but yet poorly adopted. We performed a subanalysis of the largest prospective series on the right parasternal acoustic windows in patients with aortic stenosis (330 consecutive) to calculate the degree of misalignment and estimate the potential outcome implication of this often-forgotten approach. The right parasternal view was highly feasible with an average estimated misalignment from the apical view of 14 ± 16 degree; in 10 cases, an estimated misalignment >40 degree. Right parasternal assessment (vs. apical alone) provided a significant reclassification from moderate to severe or even very-severe aortic valve stenosis. Considering a wellestablished survival benefit provided by either percutaneous or surgical valve replacement in patients with severe aortic stenosis the reclassification would result in approximately 1 life-year saved for every 30–35 patients in whom parasternal view were effectively utilized.

Context.— Vaping is the inhalation of heated aerosol from a small battery-powered device as a method to deliver nicotine or other substances. A recent outbreak of severe respiratory illness primarily in the United States has put a spotlight on vaping and its potential risks. Objective.— To familiarize pathologists with vaping, the cytologic and histopathologic features of vaping-associated acute lung injury, and the role of pathology in this diagnosis. Data Sources.— A targeted literature review was performed. Conclusions.— Most cases of vaping-associated lung injury have been linked to vaping products containing tetrahydrocannabinol or other cannabinoids. Lung biopsies show a spectrum of nonspecific acute lung injury patterns (organizing pneumonia, diffuse alveolar damage, acute fibrinous, and organizing pneumonia, or combinations of the above), accompanied by prominent, foamy macrophage accumulation. Injury is usually accentuated around small airways. Lipid-laden macrophages can be identified in bronchioloalveolar lavage fluid in most patients and these can be highlighted using lipid stains, such as oil red O, but the clinical utility of this finding remains unclear, as lipid-laden macrophages can be seen in a wide variety of processes and should not be relied upon to make the diagnosis. Classic histologic features of exogenous lipoid pneumonia have not been identified in tissue samples. Lightly pigmented macrophages, similar to those seen with traditional cigarette smoking, are present in some cases but are usually a minor feature. To date, no specific pathologic features for vaping-related injury have been identified, and it remains a diagnosis of exclusion that requires clinicopathologic correlation.