Outcomes in Patients with Vogt-Koyanagi-Harada Disease from the First-line Antimetabolites for Steroid-sparing Treatment Uveitis Trial.

PURPOSE: To compare the effectiveness of methotrexate (MTX) and mycophenolate mofetil (MMF) in achieving corticosteroid-sparing control of uveitis in patients with Vogt-Koyanagi-Harada (VKH) disease. METHODS: A subanalysis of patients with VKH from the First-line Antimetabolites as Steroid-sparing Treatment (FAST) Uveitis Trial, a randomized, observer-masked, comparative effectiveness trial, with comparisons by treatment (MTX versus MMF) and disease stage (acute versus chronic). Individuals with noninfectious uveitis were placed on a standardized corticosteroid taper and block randomized 1:1 to either 25mg weekly oral MTX or 1.5g twice daily oral MMF. The primary outcome was treatment success defined by corticosteroid-sparing control of uveitis at 6 months. Additional outcomes included change in best spectacle-corrected visual acuity (BSCVA), retinal central subfield thickness (CST), and resolution of serous retinal detachment (SRD). RESULTS: Ninety-three out of 216 enrolled patients had VKH; 49 patients were randomized to MTX and 44 to MMF, of which 85 patients (46 on MTX, 39 on MMF) contributed to the primary outcome. There was no significant difference in treatment success by antimetabolite (80.4% for MTX compared to 64.1% for MMF; P=.12) or in BSCVA improvement (P=.78). Methotrexate was superior to MMF in reducing CST (P=.003) and resolving SRD (P=.02). There was no significant difference in treatment success by disease stage (P=.25), but patients with acute VKH had greater improvement in BSCVA (P<.001) and reduction of CST (P=.02) than chronic VKH patients. CONCLUSIONS: MTX and MMF have comparable outcomes as corticosteroid-sparing immunosuppressive therapies for VKH. Visual acuity improvement was greater in acute vs chronic VKH. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT00182929.

D-Transposition of Great Arteries With Infective Endocarditis and Congestive Cardiac Failure: A Case Report.

Embryological misalignment between the aorta and pulmonary trunk gives rise to the congenital anomaly of the heart known as transposition of the great arteries (TGA). TGA is a type of parallel circulation, where the heart pumps oxygenated blood from the left ventricle into the pulmonary trunk. The deoxygenated blood from the right ventricle is circulated into the body as it pumps blood into the aorta. This type of parallel circulation is not compatible with life unless there is communication between oxygenated and deoxygenated blood. The presence of a ventricular septal defect (VSD) or patent ductus arteriosus (PDA) in TGA patients serves as this communication. Cyanosis in the first month of life is the most common presenting feature. We had a five-and-a-half-year-old male child presenting with cyanosis and congestive cardiac failure (CCF), along with infective endocarditis with mitral valve regurgitation, which is an unusual complication of dextro-TGA (d-TGA) with pulmonary stenosis (PS) with VSD.

Correlation of Platelet Parameters With the Severity of Thrombocytopenia in Dengue Fever in Children Aged Less Than 18 Years at a Tertiary Care Centre: A Cross-Sectional Study.

Introduction Dengue is a tropical viral disease caused by dengue virus with varied severity ranging from dengue fever to dengue shock syndrome. In dengue infection, there is thrombocytopenia with platelet activation. According to various proposed theories, activation of platelets during thrombocytopenia leads to changes in platelet parameters like mean platelet volume (MPV), platelet distribution width (PDW), plateletcrit (PCT), and platelet index (PI). So, this study was conducted to correlate platelet parameters with the severity of thrombocytopenia in children with dengue fever at a tertiary care hospital.  Methods An observational cross-sectional study was conducted on 72 children below 18 years admitted with dengue infection at a tertiary care hospital. All 72 patients were divided into three groups depending on platelet count. Group I included individuals with a platelet count less than 50000/mm3, while group II comprised patients with platelet counts ranging between 50001/mm3 and 100000/mm3, and group III encompassed individuals with platelet counts exceeding 100001/mm3. Platelet parameters like MPV, PDW, PCT, and PI were analyzed on day one and day three of admission. These parameters on day one and day three were correlated with the severity of thrombocytopenia in all three groups. Results PCT values on day one and day three were statistically significant (p<0.05) in all three groups with p-value <0.001 with profound positive correlation, which means PCT value decreases with increasing severity of thrombocytopenia. PI in group I was statistically significant on day one (p=0.009) but not on day three (p=0.063). PI in group II was statistically significant (p<0.05) on day three (p=0.002), while in group III, PI was significant statistically on day one (p<0.001). MPV in group I, on day one (p=0.006) and in group II, on day three (p= 0.049) were statistically significant (p<0.05). PDW was statistically significant only on day one (p=0.031) in group I, while was not significant in groups II and III. Conclusion MPV, PDW, and PCT increase with a decrease in platelet count, whereas there is an increase in PI. These platelet indices could be used to predict the severity of thrombocytopenia and severity of the dengue fever. Along with MPV and PDW, PCT could be used to assess the severity of the disease progression.

Acute neuroretinitis as a delayed manifestation of tubulointerstitial nephritis and uveitis syndrome.

Purpose: Tubulointerstitial nephritis syndrome with uveitis (TINU) is a rare, acquired syndrome characterized by interstitial nephritis with bilateral uveitis. We report a case of TINU with typical bilateral anterior uveitis complicated by an atypical, delayed-onset neuroretinitis in a 12-year old patient. Observation: A 12-year-old female with a 21-month history of TINU featuring chronic bilateral anterior uveitis presented with one week of blurred vision in her left eye. On exam she was found to have new-onset disc edema in the right eye and neuroretinitis in the left eye. After a negative infectious disease workup, the patient was treated with a course of intravenous (IV) solumedrol with prednisone taper and advancement of her systemic immunosuppression. In follow up she demonstrated resolution of her disc edema and neuroretinitis with improved visual acuity and clinical exam. Conclusion: This case stresses the importance of monitoring for additional ocular manifestations including neuroretinitis years after the onset of anterior uveitis in TINU. In comparison to the two published cases of TINU with neuroretinitis, this case shares features of uveitis progression, and thus highlights the value of further description of TINU-associated neuroretinitis.

High frequencies of alpha common cold coronavirus/SARS-CoV-2 cross-reactive functional CD4+ and CD8+ memory T cells are associated with protection from symptomatic and fatal SARS-CoV-2 infections in unvaccinated COVID-19 patients.

Background: Cross-reactive SARS-CoV-2-specific memory CD4+ and CD8+ T cells are present in up to 50% of unexposed, pre-pandemic, healthy individuals (UPPHIs). However, the characteristics of cross-reactive memory CD4+ and CD8+ T cells associated with subsequent protection of asymptomatic coronavirus disease 2019 (COVID-19) patients (i.e., unvaccinated individuals who never develop any COVID-19 symptoms despite being infected with SARS-CoV-2) remains to be fully elucidated. Methods: This study compares the antigen specificity, frequency, phenotype, and function of cross-reactive memory CD4+ and CD8+ T cells between common cold coronaviruses (CCCs) and SARS-CoV-2. T-cell responses against genome-wide conserved epitopes were studied early in the disease course in a cohort of 147 unvaccinated COVID-19 patients who were divided into six groups based on the severity of their symptoms. Results: Compared to severely ill COVID-19 patients and patients with fatal COVID-19 outcomes, the asymptomatic COVID-19 patients displayed significantly: (i) higher rates of co-infection with the 229E alpha species of CCCs (α-CCC-229E); (ii) higher frequencies of cross-reactive functional CD134+CD137+CD4+ and CD134+CD137+CD8+ T cells that cross-recognized conserved epitopes from α-CCCs and SARS-CoV-2 structural, non-structural, and accessory proteins; and (iii) lower frequencies of CCCs/SARS-CoV-2 cross-reactive exhausted PD-1+TIM3+TIGIT+CTLA4+CD4+ and PD-1+TIM3+TIGIT+CTLA4+CD8+ T cells, detected both ex vivo and in vitro. Conclusions: These findings (i) support a crucial role of functional, poly-antigenic α-CCCs/SARS-CoV-2 cross-reactive memory CD4+ and CD8+ T cells, induced following previous CCCs seasonal exposures, in protection against subsequent severe COVID-19 disease and (ii) provide critical insights into developing broadly protective, multi-antigen, CD4+, and CD8+ T-cell-based, universal pan-Coronavirus vaccines capable of conferring cross-species protection.

Cross-protection induced by highly conserved human B, CD4+, and CD8+ T-cell epitopes-based vaccine against severe infection, disease, and death caused by multiple SARS-CoV-2 variants of concern.

Background: The coronavirus disease 2019 (COVID-19) pandemic has created one of the largest global health crises in almost a century. Although the current rate of Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infections has decreased significantly, the long-term outlook of COVID-19 remains a serious cause of morbidity and mortality worldwide, with the mortality rate still substantially surpassing even that recorded for influenza viruses. The continued emergence of SARS-CoV-2 variants of concern (VOCs), including multiple heavily mutated Omicron sub-variants, has prolonged the COVID-19 pandemic and underscores the urgent need for a next-generation vaccine that will protect from multiple SARS-CoV-2 VOCs. Methods: We designed a multi-epitope-based coronavirus vaccine that incorporated B, CD4+, and CD8+ T- cell epitopes conserved among all known SARS-CoV-2 VOCs and selectively recognized by CD8+ and CD4+ T-cells from asymptomatic COVID-19 patients irrespective of VOC infection. The safety, immunogenicity, and cross-protective immunity of this pan-variant SARS-CoV-2 vaccine were studied against six VOCs using an innovative triple transgenic h-ACE-2-HLA-A2/DR mouse model. Results: The pan-variant SARS-CoV-2 vaccine (i) is safe , (ii) induces high frequencies of lung-resident functional CD8+ and CD4+ TEM and TRM cells , and (iii) provides robust protection against morbidity and virus replication. COVID-19-related lung pathology and death were caused by six SARS-CoV-2 VOCs: Alpha (B.1.1.7), Beta (B.1.351), Gamma or P1 (B.1.1.28.1), Delta (lineage B.1.617.2), and Omicron (B.1.1.529). Conclusion: A multi-epitope pan-variant SARS-CoV-2 vaccine bearing conserved human B- and T- cell epitopes from structural and non-structural SARS-CoV-2 antigens induced cross-protective immunity that facilitated virus clearance, and reduced morbidity, COVID-19-related lung pathology, and death caused by multiple SARS-CoV-2 VOCs.

Risk of Herpes Zoster Ophthalmicus Recurrence After Recombinant Zoster Vaccination.

Importance: The recombinant zoster vaccine (RZV) is currently recommended for immunocompetent adults aged 50 years or older and immunocompromised adults aged 19 years or older and is effective in preventing herpes zoster ophthalmicus (HZO). However, questions about the safety of RZV in patients with a history of HZO remain. Objective: To evaluate whether there is an increased risk of HZO recurrence after RZV in patients with a history of HZO. Design, Setting, and Participants: This retrospective cohort study used medical and outpatient pharmacy claims data for commercial and Medicare Advantage enrollees from the Optum Labs Data Warehouse. Patients with incident HZO from January 1, 2010, to December 31, 2021, were identified; the study period ended on March 31, 2022. The vaccinated group consisted of patients with at least 1 dose of RZV more than 90 days following the initial HZO diagnosis. The unvaccinated group consisted of patients without any record of RZV in the study period. Vaccinated and unvaccinated patients were matched using exact k:1 matching without replacement. Exposure: Recombinant zoster vaccination. Main Outcomes and Measures: The main outcome was the number of HZO recurrences with and without RZV exposure. Results: A total of 16 408 patients were included in the matched analysis, of whom 12 762 were unvaccinated (7806 [61.2%] female; mean [SD] age at diagnosis, 68.8 [10.3] years) and 3646 were vaccinated (2268 [62.2%] female; mean [SD] age at diagnosis, 67.4 [9.8] years). Within the primary risk period of 56 days after the index date (ie, the start of follow-up for the outcome), the incidence of HZO recurrence after any RZV exposure was 37.7 per 1000 person-years compared with 26.2 per 1000 person-years in the unexposed group. After controlling for race and ethnicity, inpatient stays, emergency department visits, concomitant vaccines, and eye care practitioner visits, the association between vaccination status and HZO exacerbation in the primary risk period had an adjusted hazard ratio for any RZV exposure of 1.64 (95% CI, 1.01-2.67; P = .04). Conclusions and Relevance: In this study, RZV exposure was associated with a higher likelihood of HZO recurrence in patients with a history of HZO compared with no RZV exposure. These findings support consideration that patients with a history of HZO may benefit from monitoring after receiving RZV in case of HZO recurrence.

A Broad-Spectrum Multi-Antigen mRNA/LNP-Based Pan-Coronavirus Vaccine Induced Potent Cross-Protective Immunity Against Infection and Disease Caused by Highly Pathogenic and Heavily Spike-Mutated SARS-CoV-2 Variants of Concern in the Syrian Hamster Model.

The first-generation Spike-alone-based COVID-19 vaccines have successfully contributed to reducing the risk of hospitalization, serious illness, and death caused by SARS-CoV-2 infections. However, waning immunity induced by these vaccines failed to prevent immune escape by many variants of concern (VOCs) that emerged from 2020 to 2024, resulting in a prolonged COVID-19 pandemic. We hypothesize that a next-generation Coronavirus (CoV) vaccine incorporating highly conserved non-Spike SARS-CoV-2 antigens would confer stronger and broader cross-protective immunity against multiple VOCs. In the present study, we identified ten non-Spike antigens that are highly conserved in 8.7 million SARS-CoV-2 strains, twenty-one VOCs, SARS-CoV, MERS-CoV, Common Cold CoVs, and animal CoVs. Seven of the 10 antigens were preferentially recognized by CD8+ and CD4+ T-cells from unvaccinated asymptomatic COVID-19 patients, irrespective of VOC infection. Three out of the seven conserved non-Spike T cell antigens belong to the early expressed Replication and Transcription Complex (RTC) region, when administered to the golden Syrian hamsters, in combination with Spike, as nucleoside-modified mRNA encapsulated in lipid nanoparticles (LNP) (i.e., combined mRNA/LNP-based pan-CoV vaccine): (i) Induced high frequencies of lung-resident antigen-specific CXCR5+CD4+ T follicular helper (TFH) cells, GzmB+CD4+ and GzmB+CD8+ cytotoxic T cells (TCYT), and CD69+IFN-γ+TNFα+CD4+ and CD69+IFN-γ+TNFα+CD8+ effector T cells (TEFF); and (ii) Reduced viral load and COVID-19-like symptoms caused by various VOCs, including the highly pathogenic B.1.617.2 Delta variant and the highly transmittable heavily Spike-mutated XBB1.5 Omicron sub-variant. The combined mRNA/LNP-based pan-CoV vaccine could be rapidly adapted for clinical use to confer broader cross-protective immunity against emerging highly mutated and pathogenic VOCs.

Global conservation status of the jawed vertebrate Tree of Life.

Human-driven extinction threatens entire lineages across the Tree of Life. Here we assess the conservation status of jawed vertebrate evolutionary history, using three policy-relevant approaches. First, we calculate an index of threat to overall evolutionary history, showing that we expect to lose 86-150 billion years (11-19%) of jawed vertebrate evolutionary history over the next 50-500 years. Second, we rank jawed vertebrate species by their EDGE scores to identify the highest priorities for species-focused conservation of evolutionary history, finding that chondrichthyans, ray-finned fish and testudines rank highest of all jawed vertebrates. Third, we assess the conservation status of jawed vertebrate families. We found that species within monotypic families are more likely to be threatened and more likely to be in decline than other species. We provide a baseline for the status of families at risk of extinction to catalyse conservation action. This work continues a trend of highlighting neglected groups-such as testudines, crocodylians, amphibians and chondrichthyans-as conservation priorities from a phylogenetic perspective.

Association between Quality of Life and Visual Acuity in a Randomized Clinical Trial of Patients with Uveitis Taking Antimetabolites.

PURPOSE: To evaluate how changes in visual acuity are associated with changes in quality of life (QoL) among patients with non-infectious uveitis taking antimetabolites. METHODS: This secondary analysis of the multicenter First-line Antimetabolites as Steroid-sparing Treatment (FAST) Uveitis Trial involves 216 participants randomized to methotrexate or mycophenolate mofetil. Vision-related (NEI-VFQ and IND-VFQ) and health-related (PCS and MCS SF-36v2) QoL and visual acuity were measured at baseline and 6-month primary endpoint. RESULTS: Visual acuity was significantly associated and correlated with all QoL measures (Spearman correlation coefficients = 0.5, 0.5, 0.3, and 0.4 for NEI-VFQ, IND-VFQ, SF-36v2 MCS and PCS, respectively). All observed changes in QoL met or exceeded the minimal clinically important difference definition on each scale. Treatment group was not significantly associated with any QoL measure. CONCLUSION: By adding insight beyond visual acuity, QoL provides a more comprehensive picture of the patient experience during uveitis treatment.Abbreviations and Acronyms: QoL = quality of life; VR-QoL = vision-related quality of life; HR-QoL = health-related quality of life; FAST = First-line Antimetabolites as Corticosteroid Sparing Treatment; NEI-VFQ = National Eye Institute Visual Functioning Questionnaire; IND-VFQ = Indian Visual Functioning Questionnaire; SF-36v2 = Medical Outcomes Study 36-Item Short Form Survey; PCS = physical component score; MCS = mental component score; 95% CI = 95% confidence interval; MCID = minimal clinically important difference.

Risk of Herpes Zoster Ophthalmicus After COVID-19 Vaccination in a Large US Health Care Claims Database.

PURPOSE: Herpes zoster ophthalmicus (HZO) after COVID-19 vaccination has been reported in numerous case studies. However, no large-scale epidemiologic studies have been conducted to date. The purpose of this study was to determine whether COVID-19 vaccination is associated with an increased risk of HZO. DESIGN: Retrospective before-and-after risk interval analysis. METHODS: RESULTS: In total, 1,959,157 patients received a dose of a COVID-19 vaccine during the study period and met eligibility criteria. A total of 80 individuals without a prior history of HZO were included in the analysis because they developed HZO in the risk or control period. Patients had a mean age of 54.0 years (SD = 12.3 years). There were 45 cases of HZO in the risk interval after COVID-19 vaccination. There was not an increased risk of HZO after vaccination with BNT162b2 (IRR = 0.90, 95% CI: 0.49-1.69, P = .74), mRNA-1273 (IRR = 0.74, 95% CI: 0.36-1.54, P = .42), or Ad26.COV2.S (IRR = 0.50, 95% CI: 0.07-2.56, P = .42). CONCLUSIONS: This study found no evidence of increased risk of HZO after COVID-19 vaccination, providing reassurance for patients and providers who may be concerned about the safety profile of the COVID-19 vaccines.

Validation of the C-DU(KE) Calculator as a Predictor of Outcomes in Patients Enrolled in Steroids for Corneal Ulcer and Mycotic Ulcer Treatment Trials.

PURPOSE: The aim of this study was to validate the C-DU(KE) calculator as a predictor of treatment outcomes on a data set derived from patients with culture-positive ulcers. METHODS: C-DU(KE) criteria were compiled from a data set consisting of 1063 cases of infectious keratitis from the Steroids for Corneal Ulcer Trial (SCUT) and Mycotic Ulcer Treatment Trial (MUTT) studies. These criteria include corticosteroid use after symptoms, visual acuity, ulcer area, fungal etiology, and elapsed time to organism-sensitive therapy. Univariate analysis was performed followed by multivariable logistic regressions on culture-exclusive and culture-inclusive models to assess for associations between the variables and outcome. The predictive probability of treatment failure, defined as the need for surgical intervention, was calculated for each study participant. Discrimination was assessed using the area under the curve for each model. RESULTS: Overall, 17.9% of SCUT/MUTT participants required surgical intervention. Univariate analysis showed that decreased visual acuity, larger ulcer area, and fungal etiology had a significant association with failed medical management. The other 2 criteria did not. In the culture-exclusive model, 2 of 3 criteria, decreased vision [odds ratio (OR) = 3.13, P < 0.001] and increased ulcer area (OR = 1.03, P < 0.001), affected outcomes. In the culture-inclusive model, 3 of 5 criteria, decreased vision (OR = 4.9, P < 0.001), ulcer area (OR = 1.02, P < 0.001), and fungal etiology (OR = 9.8, P < 0.001), affected results. The area under the curves were 0.784 for the culture-exclusive model and 0.846 for the culture-inclusive model which were comparable to the original study. CONCLUSIONS: The C-DU(KE) calculator is generalizable to a study population from large international studies primarily taking place in India. These results support its use as a risk stratification tool assisting ophthalmologists in patient management.

Practice Patterns in the Initial Management of Herpes Zoster Ophthalmicus in the United States.

PURPOSE: The aims of this study were to examine the trends in the initial management of herpes zoster ophthalmicus (HZO) in the United States from 2010 to 2018 and compare them with the treatment preferences of corneal specialists. METHODS: A retrospective, observational deidentified cohort study was conducted on individuals enrolled in the OptumLabs Data Warehouse who had a new diagnosis of HZO from 1/1/2010 to 12/31/2018. An online survey ascertaining HZO management perspectives was distributed to The Cornea Society listserv. The main outcome assessed was proportion of cases with systemic antiviral prescriptions, eye care provider involvement, and follow-up visits after the initial HZO diagnosis. RESULTS: Approximately 50% of patients received systemic antivirals the day of initial HZO diagnosis or within 7 days (45.6% and 53.7%, respectively). Most initial diagnoses were made by ophthalmologists (45.0%), followed by optometrists (19.2%). Referral rate to ophthalmology within a year of initial diagnosis was 38.6%. 48.7% cases had at least 1 follow-up visit with any type of provider within 30 days. Our survey of corneal specialists found 97% would prescribe systemic antivirals to those with ocular involvement, but 66% would prescribe antivirals to those without ocular or eyelid involvement. Seventy percent supported all patients having follow-up with an eye care provider within a month. CONCLUSIONS: HZO antiviral therapies seem to be underprescribed in the United States, referral rates to ophthalmology are low, and follow-up is suboptimal, which are not aligned with recommendations from corneal specialists. More research is needed to establish standardized guidelines for treatment, referral, and follow-up with ophthalmology for HZO.

Immunosuppressive Medications and COVID-19 Outcomes in Patients with Noninfectious Uveitis in the Era of COVID-19 Vaccinations.

Purpose: To determine the risk of coronavirus disease 2019 (COVID-19) infection, hospitalization, and death in the era of COVID-19 vaccination among patients with noninfectious uveitis (NIU) taking immunosuppressive therapies. Design: Retrospective cohort study from July 1, 2021, to June 30, 2022, using data from the Optum Labs Data Warehouse (OLDW) de-identified claims database. Participants: Patients with a diagnosis of NIU from January 1, 2017, and who had ≥ 1 year of continuous enrollment in the OLDW. Methods: Incidence rates (IRs) were calculated for each COVID-19 outcome. Unadjusted and adjusted hazard ratios (HRs) were estimated for each variable and COVID-19 outcome using Cox proportional hazards models with time-updated dichotomous indicators for outpatient immunosuppressive medication exposure. To assess the dose-dependent effect of systemic corticosteroid (SC) exposure, the average daily dose of prednisone over the exposed interval was included in the adjusted models. Main Outcome Measures: Hazard ratios and IRs for COVID-19 infection, hospitalization, and death. Results: This study included 62 209 patients with NIU. A total of 12 895 (20.7%) were exposed to SCs during the risk period. Incidence rates were increased when exposed to SCs versus unexposed for all COVID-19 outcomes. Incidence rates were also increased for all COVID-19 outcomes when exposed to SCs without COVID-19 vaccination versus exposed to SCs with ≥ 1 vaccination. In adjusted models, SCs were associated with increased risk of COVID-19 infection (HR, 3.57; 95% confidence interval [CI], 3.24-3.93; P < 0.0001), hospitalization (HR, 2.75; 95% CI, 2.07-3.65; P < 0.0001), and death (HR, 2.49; 95% CI 1.29-4.82; P = 0.007). Incremental increases in SC dose were associated with a greater risk for all outcomes. Disease-modifying anti-rheumatic drugs were associated with a decreased risk of infection (HR, 0.84; 95% CI, 0.74-0.96; P = 0.01), and tumor necrosis factor-α inhibitors were associated with an increased risk of infection (HR, 1.18; 95% CI, 1.01-1.39; P = 0.04). Conclusions: Systemic corticosteroid exposure continues to be associated with greater risk of COVID-19 infection, hospitalization, and death among patients with NIU in an era of widespread COVID-19 vaccination. Unvaccinated individuals who are exposed to immunosuppressive treatments have a greater risk of severe outcomes. Coronavirus disease 2019 vaccination should be strongly encouraged in these patients. Financial Disclosures: Proprietary or commercial disclosure may be found in the Footnotes and Disclosures at the end of this article.

Reconstruction in Salvage Surgery for Head and Neck Cancers.

Introduction: Salvage surgery is the treatment option in recurrences and second primary tumors. This paper aimed to study the options and outcomes of reconstruction and the predictors of poor reconstructive outcomes in salvage surgery for head and neck cancers. Study Design: This is a retrospective study of all patients who underwent reconstructive flap surgery as part of salvage surgery for head and neck cancers between the years 2004 and 2017. Methods: The initial treatment may be single modality radiotherapy or surgery or multimodality with combinations of surgery, radiotherapy, and chemotherapy. Any pathology that required surgical salvage was included. Any procedures done purely as reconstructive surgery were excluded. Predictor variables included demographical, clinical, and treatment factors. The outcome parameter was the occurrence of any flap-related complication or not. The complications and morbidity related to the procedures are reported. Results: Ninety-three patients underwent loco-regional flaps (LRF group), and 100 had free flaps (FF group). Pectoralis major flap was the commonest flap used in 68 patients (73.1%). Anterolateral thigh (ALT) flap was the commonest free flap and comprised 41% of the FF group. Any skin-related complication was seen in 35 patients (37.6%) and 41 (41%), respectively, in LRF and FF subsets. Any flap-related complication was seen in 16 patients (17.2%) and 29 patients (29%), respectively, in LRF and FF subsets. A summary measure "any one of the complications" was seen in 46 (49.5%) and 57 (57%), respectively, in LRF and FF subsets. Univariate and multivariate analysis for any flap-related complication identified no statistically significant predictor. Conclusions: Soft tissue flaps were preferred in salvage reconstruction, though the defects had a bony component. In the microvascular free flap reconstruction era, pectoralis major flap has shifted its role from a "workhorse flap" to a "salvage flap." About half of the patients develop some complications. Flap-related complications are also common. In salvage surgery, it is important that an appropriate flap is selected, suitable for the setting, according to the indications, neck, and patient conditions.

Conserving avian evolutionary history can effectively safeguard future benefits for people.

Phylogenetic diversity (PD)-the evolutionary history of a set of species-is conceptually linked to the maintenance of yet-to-be-discovered benefits from biodiversity or "option value." We used global phylogenetic and utilization data for birds to test the PD option value link, under the assumption that the performance of sets of PD-maximizing species at capturing known benefits is analogous to selecting the same species at a point in human history before these benefits were realized. PD performed better than random at capturing utilized bird species across 60% of tests, with performance linked to the phylogenetic dispersion and prevalence of each utilization category. Prioritizing threatened species for conservation by the PD they encapsulate performs comparably to prioritizing by their functional distinctiveness. However, species selected by each metric show low overlap, indicating that we should conserve both components of biodiversity to effectively conserve a variety of uses. Our findings provide empirical support for the link between evolutionary history and benefits for future generations.