Intravenous Immunoglobulin Plus Methylprednisolone Mitigate Respiratory Morbidity in Coronavirus Disease 2019.

Dysregulated neutrophil and platelet interactions mediate immunothrombosis and cause lung injury in coronavirus disease 2019. IV immunoglobulin modulates neutrophil activation through FcγRIII binding. We hypothesized that early therapy with IV immunoglobulin would abrogate immunothrombosis and improve oxygenation and reduce progression to mechanical ventilation in coronavirus disease 2019 pneumonia. DESIGN: Prospective randomized open label. SETTING: Inpatient hospital. PATIENTS AND INTERVENTION: Hypoxic subjects with coronavirus disease 2019 pneumonia were randomized 1:1 to receive standard of care plus IV immunoglobulin 0.5 g/kg/d with methylprednisolone 40 mg 30 minutes before infusion for 3 days versus standard of care alone. MAIN RESULTS: Sixteen subjects received IV immunoglobulin and 17 standard of care. Median ages were 51 and 58 years for standard of care and IV immunoglobulin, respectively. Acute Physiology and Chronic Health Evaluation II and Charlson comorbidity scores were similar for IV immunoglobulin and standard of care. Seven standard of care versus two IV immunoglobulin subjects required mechanical ventilation (p = 0.12, Fisher exact test). Among subjects with A-a gradient of greater than 200 mm Hg at enrollment, the IV immunoglobulin group showed: 1) a lower rate of progression to requiring mechanical ventilation (2/14 vs 7/12, p = 0.038 Fisher exact test), 2) shorter median hospital length of stay (11 vs 19 d, p = 0.01 Mann Whitney U test), 3) shorter median ICU stay (2.5 vs 12.5 d, p = 0.006 Mann Whitey U test), and 4) greater improvement in Pao2/Fio2 at 7 days (median [range] change from time of enrollment +131 [+35 to +330] vs +44·5 [-115 to +157], p = 0.01, Mann Whitney U test) than standard of care. Pao2/Fio2 improvement at day 7 was significantly less for the standard of care patients who received glucocorticoid therapy than those in the IV immunoglobulin arm (p = 0.0057, Mann Whiney U test). CONCLUSIONS: This pilot study showed that IV immunoglobulin significantly improved hypoxia and reduced hospital length of stay and progression to mechanical ventilation in coronavirus disease 2019 patients with A-a gradient greater than 200 mm Hg. A phase 3 multicenter randomized double-blinded clinical trial is under way to validate these findings.

Kinetics of maternal pertussis-specific antibodies in infants of mothers vaccinated with tetanus, diphtheria and acellular pertussis (Tdap) during pregnancy.

BACKGROUND: Kinetics of Tdap-induced maternally-derived antibodies in infants are poorly understood. Pre-Tdap era data suggest that maternal pertussis antibodies in infants have a half-life of approximately 5-6 weeks. METHODS: 34 mother-infant pairs had blood collected before maternal Tdap vaccination, 4 weeks later, at delivery (maternal and cord), and at infant ages 3 and 6 weeks from June 2014-March 2015. Immunoglobulin G (IgG) to pertussis toxin (PT), filamentous hemagglutinin (FHA), fimbrial proteins (FIM) and pertactin (PRN) was quantified by multiplex luminex assay (IU/ml). Geometric mean concentrations (GMCs) with 95% confidence intervals (C.I.) and half-life of pertussis antibodies were calculated. RESULTS: Tdap was administered to 34 women (mean age 31.1 years) at mean gestation 30.7 weeks (28-32.7). Mean neonatal gestation was 39.1 weeks (36-41.1) and mean birthweight was 3379 g (2580-4584). Four weeks post-Tdap vaccination, maternal pertussis-specific IgG GMCs increased ≥4-fold in 59%, 41%, 29% and 44% of women for PT, FHA, FIM and PRN, respectively, and then waned. The transplacental transport ratio of pertussis antibodies was 1.35 for PT, 1.41 for FHA, 1.31 for FIM and 1.36 for PRN. Between birth and age 6 weeks, infant serum GMC for PT-specific IgG decreased from 55.1 IU/mL (38.6-78.6) to 21.1 IU/ml (14.7-30.2), and the proportion of infants with PT levels ≥10 IU/ml fell from 97% to 67%. Half-life of pertussis-specific IgG in infants in days was 29.4 (95% CI 27.3-31.7) for PT, 29.8 (95% CI 27.7-32.2) for FHA, 31.2 (95% CI 28.9-33.7) for PRN, and 35.8 (95% CI 30.1-44.3) for FIM. CONCLUSION: The half-life of pertussis-specific antibodies in infants induced by maternal Tdap vaccination (29-36 days) is shorter than previously reported. Understanding how the durability of passively-acquired antibodies impacts infant susceptibility to pertussis and response to primary vaccination is critical to refine prevention strategies.

Clinical outcomes and adherence to topical corticosteroid therapy in women with vulvar lichen sclerosus: A retrospective cohort study.

BACKGROUND: Vulvar lichen sclerosus is a progressive dermatitis with significant itching, pain, and sexual dysfunction. OBJECTIVE: To investigate topical steroid use and clinical improvement across multiple specialties. METHODS: Retrospective cohort study at dermatology, gynecology, and vulvovaginal specialty clinics from 2012 to 2017. Descriptive statistics and panel logistic regression were performed. RESULTS: A total of 333 women attended 1525 visits (median 6/patient; range, 1-24 visits). Patients used steroids exactly as prescribed at 66% of visits, less than prescribed at 26%, and not at all at 8%. Versus no use, exact use improved symptoms (odds ratio [OR], 4.6; 95% confidence interval [CI], 2.2-9.6) and physical examination findings (OR, 6.9; 95% CI, 2.7-17.6) more than infrequent steroid use (symptoms: OR, 2.5; 95% CI, 1.2-5.4; physical examination findings: OR, 4.2; 95% CI, 1.6-11.0). Sexual activity status was noted in 93% of vulvovaginal, 29% of gynecology, and 0% of dermatology visits. At intake, 42% of women were sexually inactive because of pain; of these, 37% became sexually active after steroid treatment. Steroid adherence was not associated with change in sexual activity. CONCLUSIONS: Women with vulvar lichen sclerosus improve more when topical steroids are used exactly as prescribed, although some improvement occurs with imperfect use. Sexual activity documentation is inconsistent, limiting quality of life follow-up.

Ramelteon for Prevention of Postoperative Delirium: A Randomized Controlled Trial in Patients Undergoing Elective Pulmonary Thromboendarterectomy.

OBJECTIVES: To assess the efficacy of ramelteon in preventing delirium, an acute neuropsychiatric condition associated with increased morbidity and mortality, in the perioperative, ICU setting. DESIGN: Parallel-arm, randomized, double-blinded, placebo-controlled trial. SETTING: Academic medical center in La Jolla, California. PATIENTS: Patients greater than or equal to 18 years undergoing elective pulmonary thromboendarterectomy. INTERVENTIONS: Ramelteon 8 mg or matching placebo starting the night prior to surgery and for a maximum of six nights while in the ICU. MEASUREMENTS AND MAIN RESULTS: Incident delirium was measured twice daily using the Confusion Assessment Method-ICU. The safety outcome was coma-free days assessed by the Richmond Agitation-Sedation Scale. One-hundred twenty participants were enrolled and analysis completed in 117. Delirium occurred in 22 of 58 patients allocated to placebo versus 19 of 59 allocated to ramelteon (relative risk, 0.8; 95% CI, 0.5-1.4; p = 0.516). Delirium duration, as assessed by the number of delirium-free days was also similar in both groups (placebo median 2 d [interquartile range, 2-3 d] vs ramelteon 3 d [2-5 d]; p = 0.181). Coma-free days was also similar between groups (placebo median 2 d [interquartile range, 1-3 d] vs ramelteon 3 d [2-4 d]; p = 0.210). We found no difference in ICU length of stay (median 4 d [interquartile range, 3-5 d] vs 4 d [3-6 d]; p = 0.349), or in-hospital mortality (four vs three deaths; relative risk ratio, 0.7; 95% CI, 0.2-3.2; p = 0.717), all placebo versus ramelteon, respectively. CONCLUSIONS: Ramelteon 8 mg did not prevent postoperative delirium in patients admitted for elective cardiac surgery.

The Female Genital Self-image Scale in Adult Women With Vulvar Lichen Sclerosus.

OBJECTIVE: There is no agreed upon standard way to measure vulvar lichen sclerosus disease severity. The Female Genital Self-Image Scale (FGSIS) is a validated survey tool assessing female genital self-image and is positively correlated with women's sexual function. A lower score represents a negative genital self-image. We evaluated the FGSIS in women with vulvar lichen sclerosus. METHODS: Women with biopsy-proven lichen sclerosus and women presenting for routine gynecologic care without lichen sclerosus matched by age were surveyed with the 7-item FGSIS. National surveys of healthy women in the United States have shown the mean 7-item FGSIS score is 21. To detect one standard deviation (20% absolute difference) between groups with a power of 80% at p < .05, 15 women would are needed in each group. RESULTS: Sixteen women with lichen sclerosus and 16 matched controls were surveyed between February and July 2018. The mean ± SD age of women with lichen sclerosus was 56.8 ± 13.5 years, 94% were white, 69% married, 81% college educated, 69% postmenopausal, and 18% on hormone replacement therapy. None of these differences were statistically different from control women. Women with vulvar lichen sclerosus had a significantly lower median 7-item FGSIS when compared with control subjects, 18 (interquartile range = 16-21) versus 25 (interquartile range = 23-27), respectively, Mann-Whitney U test, p < .001. CONCLUSIONS: Women with vulvar lichen sclerosus have a lower score on the 7-item Female Genital Self-Image Scale compared with healthy controls.

Prevalence and Capsular Types of Group B Streptococci Colonizing Indian Women Living in the United States.

Group B streptococcal rectovaginal colonization prevalence in women of Indian descent living in the United States was 24.7% comparable with US rates but higher than rates reported from India. The capsular polysaccharide types were distinct in that type V was most common and 33% of group B streptococcal strains were nontypeable.

Factors and outcomes associated with inpatient cardiac arrest following emergent endotracheal intubation.

BACKGROUND: Inpatient peri-intubation cardiac arrest (PICA) following emergent endotracheal intubation (ETI) is an uncommon but potentially preventable type of cardiac arrest (CA). Limited published data exist describing factors associated with inpatient PICA and patient outcomes. This study identifies risk factors associated with PICA among hospitalized patients emergently intubated out of the operating room and compares PICA to other types of inpatient CA. METHODS: Retrospective case-control study of patients at our institution over a five-year period. Cases were defined as inpatients emergently intubated outside of the operating room that experienced cardiac arrest within 20min after ETI. The control group consisted of inpatients emergently intubated out of the operating room without CA. Predictors of PICA were identified through univariate and multivariate analysis. Clinical outcomes were compared between PICA and other inpatient CAs, identified through a prospectively enrolled CA registry at our institution. RESULTS: 29 episodes of PICA occurred over 5 years, accounting for 5% of all inpatient arrests. Shock index ≥1.0, intubation within one hour of nursing shift change, and use of succinylcholine were independently associated with PICA. Sustained ROSC, survival to discharge, and neurocognitive outcome did not differ significantly between groups. CONCLUSION: Patients outcomes following PICA were comparable to other causes of inpatient CA. Potentially modifiable factors were associated with PICA. Hemodynamic resuscitation, optimized staffing strategies, and possible avoidance of succinylcholine were associated with decreased risk of PICA. Clinical trials testing targeted strategies to optimize peri-intubation care are needed to identify effective interventions to prevent this potentially avoidable type of CA.

Genital Lichen Sclerosus and its Mimics.

A variety of disorders may be confused with vulvar or genital lichen sclerosus, as they can share several common features. This article discusses diagnosis, workup, and management of vulvar lichen sclerosus with specific attention on distinguishing it from other dermatologic mimics.

Respiratory failure due to lung involvement with adult T-cell leukemia/lymphoma: case report and review of literature.

Acute adult T-cellleukemia/lymphoma (ATLL) is a hematologic malignancy that usually entails a poor prognosis; median survival is only six months. Significant immunosuppression is commonly seen in these patients. Lung involvement in ATLL is usually documented either radiographically or as an autopsy finding. Few proven cases of ante mortem extensive lung infiltration have been described in the scientific literature. We present a fatal case of acute respiratory failure as a result of histologically proven lung infiltration by malignant lymphocytes in a patientwith acuteATLL. Although the most common cause of death i n patients with ATLL is respiratory failure in the setting of an infectious process, it should be kept in mind that patients with ATLL with acute respiratory failure may have malignant lung infiltration as a potential cause.