Citations

BACKGROUND: Early reports associating severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) infection with adverse pregnancy outcomes were biased by including only women with severe disease without controls. The Society for Obstetric Anesthesia and Perinatology (SOAP) coronavirus disease 2019 (COVID-19) registry was created to compare peripartum outcomes and anesthetic utilization in women with and without SARS-CoV-2 infection delivering at institutions with widespread testing. METHODS: Deliveries from 14 US medical centers, from March 19 to May 31, 2020, were included. Peripartum infection was defined as a positive SARS-CoV-2 polymerase chain reaction test within 14 days of delivery. Consecutive SARS-CoV-2–infected patients with randomly selected control patients were sampled (1:2 ratio) with controls delivering during the same day without a positive test. Outcomes were obstetric (eg, delivery mode, hypertensive disorders of pregnancy, and delivery <37 weeks), an adverse neonatal outcome composite measure (primary), and anesthetic utilization (eg, neuraxial labor analgesia and anesthesia). Outcomes were analyzed using generalized estimating equations to account for clustering within centers. Sensitivity analyses compared symptomatic and asymptomatic patients to controls. RESULTS: One thousand four hundred fifty four peripartum women were included: 490 with SARS-CoV-2 infection (176 [35.9%] symptomatic) and 964 were controls. SARS-CoV-2 patients were slightly younger, more likely nonnulliparous, nonwhite, and Hispanic than controls. They were more likely to have diabetes, obesity, or cardiac disease and less likely to have autoimmune disease. After adjustment for confounders, individuals experiencing SARS-CoV-2 infection exhibited an increased risk for delivery <37 weeks of gestation compared to controls, 73 (14.8%) vs 98 (10.2%) (adjusted odds ratio [aOR], 1.47; 95% confidence interval [CI], 1.03–2.09). Effect estimates for other obstetric outcomes and the neonatal composite outcome measure were not meaningfully different between SARS-CoV-2 patients versus controls. In sensitivity analyses, compared to controls, symptomatic SARS-CoV-2 patients exhibited increases in cesarean delivery (aOR, 1.57; 95% CI, 1.09–2.27), postpartum length of stay (aOR, 1.89; 95% CI, 1.18–2.60), and delivery <37 weeks of gestation (aOR, 2.08; 95% CI, 1.29–3.36). These adverse outcomes were not found in asymptomatic women versus controls. SARS-CoV-2 patients (asymptomatic and symptomatic) were less likely to receive neuraxial labor analgesia (aOR, 0.52; 95% CI, 0.35–0.75) and more likely to receive general anesthesia for cesarean delivery (aOR, 3.69; 95% CI, 1.40–9.74) due to maternal respiratory failure. CONCLUSIONS: In this large, multicenter US cohort study of women with and without peripartum SARS-CoV-2 infection, differences in obstetric and neonatal outcomes seem to be mostly driven by symptomatic patients. Lower utilization of neuraxial analgesia in laboring patients with asymptomatic or symptomatic infection compared to patients without infection requires further investigation.

Abstract Introduction Burn and traumatic limb injuries with exposed bone/tendon typically require surgical flaps or amputations for healing. Some burn patients are not candidates for these invasive techniques. Placental amniotic membrane has been used as a wound dressing for more than 100 years and may offer an alternative to flaps and/or amputations. Processed dehydrated human amnion/chorion membrane (dHACM), from human placental tissue, contains type 1 human collagen as well as non-viable cells and 285 identified regulatory proteins including growth factors, chemokines, cytokines, metalloproteinases, and other tissue growth and inflammatory mediators. dHACM has been successfully used as a dressing for wound ulcers, burns, donor sites, & surgical debridement. This study reports the use of dHCAM as a limb salvage tool in four patients with severe injuries. Methods This is a retrospective case series of patients suffering severe lower extremity injury with bone/tendon exposure that had applied dHACM/dHCM over or packed (depending on wound depth), then covered with 3% bismuth tribromophenate petrolatum dressing & glycerol/ hydroxyethylcellulose lubricant. Negative pressure wound therapy (NPWT) was initiated; wound re-evaluation occurred in seven days. dHACM/dHCM was reapplied if required (bone still exposed). Results There were 3 males and 1 female with three burns and one NSTI. The mean±sd (median) age was 58±23 (61) years; % total burn surface area 3±3 (2); length of hospital stay 48±30 (40) days; number of tangential excisions & debridements 6.5±1 (6.5); days from admission to product application 49±47 (34) and discharge 24±19 (19) days; negative pressure wound therapy (NPWT) 53±6 (56) days. All four patients continued treatment upon discharge with clinic visits and home NPWT. All recovered with good results and no complications. Treatment may be continued with NPWT therapy at home or in a skilled nursing facility. Patients healed after two to three dHACM/dHCM applications and did not require leg or foot amputations. Conclusions In select limb salvage cases, dHACM/HCM may be a promising alternative to extremity amputations, tissue transfer flaps or other techniques for secondary intention healing of wounds with bone/tendon exposure.

Abstract Proton therapy has a distinct dosimetric advantage over conventional photon therapy due to its Bragg peak profile. This allows greater accuracy in dose delivery and dose conformation to the target, however it requires greater precision in setup, delivery and for quality assurance (QA) procedures. The AAPM TG 224 report recommends daily range and spot position checks with tolerance on the order of a millimetre. Daily QA systems must therefore be efficient for daily use and be capable of sub-millimetre precision however few suitable commercial systems are available. In this work, a compact, real-time daily QA system is optimised and characterised for proton range verification using an ad-hoc Geant4 simulation. The system is comprised of a monolithic silicon diode array detector embedded in a perspex phantom. The detector is orientated at an angular offset to the incident proton beam to allow range in perspex to be determined for flat proton fields. The accuracy of the system for proton range in perspex measurements was experimentally evaluated over the full range of clinical proton energies. The mean R 100 , R 90 and R 80 ranges measured with the system were accurate within ±0.6 mm of simulated ranges in a perspex phantom for all energies assessed. This system allows real-time read-out of individual detector channels also making it appropriate for temporal beam delivery diagnostics and for spot position monitoring along one axis. The system presented provides a suitable, economical and efficient alternative for daily QA in proton therapy.

ObjectiveDiagnostic delay in human papillomavirus–associated oropharynx squamous cell carcinoma (HPV(+)OPSCC) is common due to nonspecific symptoms. We aim to describe the disease burden and oncologic outcomes of patients with HPV(+)OPSCC diagnosed >12 months after symptom onset.Study DesignThis is a retrospective cohort study of HPV(+)OPSCC patients receiving intent‐to‐cure treatment (including surgery ± adjuvant therapy or primary chemoradiation).Setting2006‐2016, tertiary care center.MethodsTumor stage was compared between patients with and without delayed diagnosis using χ2 tests. Kaplan‐Meier survival analysis with univariate and multivariable Cox regressions were used to determine the effect of diagnostic delay on oncologic outcomes.ResultsIn total, 664 patients were included. Compared to patients diagnosed <12 months from symptom onset (n = 601), those diagnosed at >12 months (n = 63) were more likely to have T4 disease and higher overall American Joint Committee on Cancer (AJCC) clinical stage at presentation (P <. 01 for both). At 5 years, rates of overall survival, cancer‐specific survival, progression‐free survival, and distant metastases–free survival in the delayed diagnosis cohort were 80%, 90%, 80%, and 89%, respectively. A >12‐month delay in diagnosis did not significantly impact overall survival (adjusted hazard ratio [aHR], 1.16; 95% CI, 0.58‐2.31), cancer‐specific survival (aHR, 0.83; 95% CI, 0.29‐2.39), progression‐free survival (aHR, 1.15; 95% CI, 0.56‐2.37), or distant metastases–free survival (aHR, 1.00; 95% CI, 0.42‐2.40) after adjusting for age, sex, and clinical AJCC stage (P >. 05 for all).ConclusionsDelayed diagnosis of HPV(+)OPSCC is associated with greater burden of disease at presentation, but oncologic outcomes remain favorable across treatment modalities. When appropriate, intent‐to‐cure therapy should be pursued despite diagnostic delay.Level of EvidenceLevel III.

Abstract BACKGROUND Trigeminal neuralgia (TN) refractory to medical management is often treated with microvascular decompression (MVD) involving the intracranial placement of Teflon. The placement of Teflon is an effective treatment, but does apply distributed pressure to the nerve and has been associated with pain recurrence. OBJECTIVE To report the rate of postoperative pain recurrence in TN patients who underwent MVD surgery using a transposition technique with fibrin glue without Teflon. METHODS Patients were eligible for our study if they were diagnosed with TN, did not have multiple sclerosis, and had an offending vessel that was identified and transposed with fibrin glue at our institution. All eligible patients were given a follow-up survey. We used a Kaplan-Meier (KM) model to estimate overall pain recurrence. RESULTS A total of 102 patients met inclusion criteria, of which 85 (83%) responded to our survey. Overall, 76 (89.4%) participants responded as having no pain recurrence. Approximately 1-yr pain-free KM estimates were 94.1% (n = 83), 5-yr pain-free KM estimates were 94.1% (n = 53), and 10-yr pain-free KM estimates were 83.0% (n = 23). CONCLUSION Treatment for TN with an MVD transposition technique using fibrin glue may avoid some cases of pain recurrence. The percentage of patients in our cohort who remained pain free at a maximum of 17 yr follow-up is on the high end of pain-free rates reported by MVD studies using Teflon. These results indicate that a transposition technique that emphasizes removing any compression near the trigeminal nerve root provides long-term pain-free rates for patients with TN.

Teplizumab treatment of nondiabetic relatives at high risk for T1D induces partially exhausted CD8 + T cells and improves beta cell function.

AbstractIntroductionThis study evaluated the diagnostic accuracy of the Cogstate Brief Battery (CBB) for mild cognitive impairment (MCI) and prodromal Alzheimer's disease (AD) in a population‐based sample.MethodsParticipants included adults ages 50+ classified as cognitively unimpaired (CU, n = 2866) or MCI (n = 226), and a subset with amyloid (A) and tau (T) positron emission tomography who were AD biomarker negative (A–T–) or had prodromal AD (A+T+).ResultsDiagnostic accuracy of the Learning/Working Memory Composite (Lrn/WM) for discriminating all CU and MCI was moderate (area under the curve [AUC] = 0.75), but improved when discriminating CU A–T– and MCI A+T+ (AUC = 0.93) and when differentiating MCI participants without AD biomarkers from those with prodromal AD (AUC = 0.86). Conventional cut‐offs yielded lower than expected sensitivity for both MCI (38%) and prodromal AD (73%).DiscussionClinical utility of the CBB for detecting MCI in a population‐based sample is lower than expected. Caution is needed when using currently available CBB normative data for clinical interpretation.

Objective An understanding of the etiologic heterogeneity of colorectal cancer (CRC) is critical for improving precision prevention, including individualized screening recommendations and the discovery of novel drug targets and repurposable drug candidates for chemoprevention. Known differences in molecular characteristics and environmental risk factors among tumors arising in different locations of the colorectum suggest partly distinct mechanisms of carcinogenesis. The extent to which the contribution of inherited genetic risk factors for CRC differs by anatomical subsite of the primary tumor has not been examined. Design To identify new anatomical subsite-specific risk loci, we performed genome-wide association study (GWAS) meta-analyses including data of 48 214 CRC cases and 64 159 controls of European ancestry. We characterised effect heterogeneity at CRC risk loci using multinomial modelling. Results We identified 13 loci that reached genome-wide significance (p<5×10 −8 ) and that were not reported by previous GWASs for overall CRC risk. Multiple lines of evidence support candidate genes at several of these loci. We detected substantial heterogeneity between anatomical subsites. Just over half (61) of 109 known and new risk variants showed no evidence for heterogeneity. In contrast, 22 variants showed association with distal CRC (including rectal cancer), but no evidence for association or an attenuated association with proximal CRC. For two loci, there was strong evidence for effects confined to proximal colon cancer. Conclusion Genetic architectures of proximal and distal CRC are partly distinct. Studies of risk factors and mechanisms of carcinogenesis, and precision prevention strategies should take into consideration the anatomical subsite of the tumour.