Total lower lip reconstruction: a review of recent advances.

PURPOSE OF REVIEW: This review describes the fundamental principles and recent advances in the reconstruction of total lower lip defects to restore peri-oral aesthetic and function. RECENT FINDINGS: Modifications to the Abbe flap and visor flap have recently been described. Recent advances to free flap techniques have focused on dynamic restoration of lower lip sling function after reconstruction. This involves the transfer of innervated or noninnervated muscle tissue to reconstruct the lower lip to restore the sphincter function of the lips. SUMMARY: The reconstructive goals for a full thickness lower lip defect are to restore a functional oral sphincter, replace mucosal and external skin, and maintain a functional size of the oral aperture. Local flap reconstruction of sub-total lower lip defects is possible, but use of local flaps for total lip reconstruction often leads to microstomia. Several static and dynamic free tissue transfer options exist for lower lip reconstruction and have been summarized in this review.

Insights into the mechanism of binding of doxorubicin and a chlorin compound with 22-mer c-Myc G quadruplex.

BACKGROUND: The interaction of small molecules with G quadruplexes is in focus due to its role in molecular recognition and therapeutic drug design. Stabilization of G-quadruplex structures in the promoter regions of oncogenes by small molecule binding has been demonstrated as a potential approach for cancer therapy. METHODS: In this study, electronic spectroscopy (ultraviolet-visible, fluorescence, circular dichroism), differential scanning calorimetry, and molecular modeling were employed to explore the interactions between the chemotherapy drug doxorubicin and a chlorin compound 5,10,15,20-tetraphenyl-[2,3]-[bis(carboxy)-methano]chlorin (H2TPC(DAC)), and the c-Myc 22-mer G quadruplex DNA. RESULTS: Spectroscopic studies indicated external binding of the compounds with partial stacking at the end quartets. Calorimetric studies and temperature dependent circular dichroism data displayed increased melting temperatures of G quadruplex structure on binding with the compounds. Circular dichroism spectra indicated that the G quadruplex structure is intact upon ligand binding. Both the compounds showed binding affinities of the order of 106 M-1. Fluorescence lifetime studies revealed static quenching as major mechanism for fluorescence quenching. Polymerase chain reaction stop assay hinted that binding of both ligands under study could inhibit the amplification of the DNA sequence. CONCLUSION: Results show that doxorubicin and H2TPC(DAC) bind to the 22-mer c-Myc quadruplex structure with good affinity and induce stability. SIGNIFICANCE: Doxorubicin and H2TPC(DAC) have demonstrated their affinity towards c-Myc G quadruplex DNA, stabilizing it and inhibiting expression and polymerization. The results can be of practical use in designing new analogs for the two compounds, which can become potent anti-cancer agents targeting the c-Myc GQ structure.

Hearing Loss and Frailty among Older Adults: The Atherosclerosis Risk in Communities Study.

OBJECTIVES: Hearing loss may contribute to frailty through cognitive and physical decline, but population-based evidence using validated measures remains scarce. We investigated the association of hearing loss with phenotypic frailty and its individual components and explored the potential protective role of hearing aid use. DESIGN: Cross-sectional study of community-dwelling older adults at visit 6 (2016-2017) of the Atherosclerosis Risk in Communities (ARIC) study, a cohort study of older adults from 4 U.S. communities (Washington County, MD; Forsyth County, NC; Jackson, MS; and Minneapolis, MN). SETTING AND PARTICIPANTS: Population-based study of 3179 participants (mean age = 79.2 years, 58.9% female). METHODS: Pure-tone audiometry at 0.5-4 kHz was used to assess unaided hearing, and the better-hearing ear's pure-tone average was categorized as follows: no [≤25 dB hearing level (HL)], mild (26-40 dB HL), and moderate or greater (>40 dB HL) hearing loss. Hearing aid use was self-reported. The Fried/physical frailty phenotype was used to categorize frailty status (robust, pre-frail, or frail). Multivariable multinomial and logistic regression models were used to study the association of hearing loss/hearing aid use with frailty status and individual frailty components, respectively. RESULTS: In our sample, 40% had mild and 27% had moderate or greater hearing loss (12% and 55% reported hearing aid use, respectively). Moderate or greater hearing loss was associated with greater odds of being pre-frail [odds ratio (OR), 1.25; 95% CI, 1.01-1.57] and frail (OR, 1.62; 95% CI, 1.06-2.47) vs robust, and greater odds of having slow gait, low physical activity, and exhaustion, compared with no hearing loss. Among those with hearing loss (>25 dB HL), compared with hearing aid users, nonusers had greater odds of being frail vs robust, and having unintentional weight loss, slow gait, and low physical activity. CONCLUSIONS AND IMPLICATIONS: Hearing loss is associated with pre-frailty and frailty. Longitudinal studies are warranted to establish if hearing aid use may prevent or delay frailty onset.

Rhinoplasty: Considerations for Patients with Facial Paralysis.

Nasal obstruction is a common sequela of flaccid facial paralysis but one that is often underaddressed surgically. Weakness of nasal musculature on the paralyzed side of the face leads to nasal valve narrowing through loss of static and dynamic nasal side wall tone as well as inferomedial displacement of the alar base. Standard rhinoplasty techniques such as alar batten grafts or flaring sutures may be used to support the nasal side wall in facial paralysis. However, to address the inferomedial alar displacement, suspension techniques are often required. Suture resuspension and fascia lata resuspension techniques are described, with modifications to each to improve longevity of the suspension.

Omicron BA.2 lineage predominance in severe acute respiratory syndrome coronavirus 2 positive cases during the third wave in North India.

Background: Recent studies on severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) reveal that Omicron variant BA.1 and sub-lineages have revived the concern over resistance to antiviral drugs and vaccine-induced immunity. The present study aims to analyze the clinical profile and genome characterization of the SARS-CoV-2 variant in eastern Uttar Pradesh (UP), North India. Methods: Whole-genome sequencing (WGS) was conducted for 146 SARS-CoV-2 samples obtained from individuals who tested coronavirus disease 2019 (COVID-19) positive between the period of 1 January 2022 and 24 February 2022, from three districts of eastern UP. The details regarding clinical and hospitalized status were captured through telephonic interviews after obtaining verbal informed consent. A maximum-likelihood phylogenetic tree was created for evolutionary analysis using MEGA7. Results: The mean age of study participants was 33.9 ± 13.1 years, with 73.5% accounting for male patients. Of the 98 cases contacted by telephone, 30 (30.6%) had a travel history (domestic/international), 16 (16.3%) reported having been infected with COVID-19 in past, 79 (80.6%) had symptoms, and seven had at least one comorbidity. Most of the sequences belonged to the Omicron variant, with BA.1 (6.2%), BA.1.1 (2.7%), BA.1.1.1 (0.7%), BA.1.1.7 (5.5%), BA.1.17.2 (0.7%), BA.1.18 (0.7%), BA.2 (30.8%), BA.2.10 (50.7%), BA.2.12 (0.7%), and B.1.617.2 (1.3%) lineages. BA.1 and BA.1.1 strains possess signature spike mutations S:A67V, S:T95I, S:R346K, S:S371L, S:G446S, S:G496S, S:T547K, S:N856K, and S:L981F, and BA.2 contains S:V213G, S:T376A, and S:D405N. Notably, ins214EPE (S1- N-Terminal domain) mutation was found in a significant number of Omicron BA.1 and sub-lineages. The overall Omicron BA.2 lineage was observed in 79.5% of women and 83.2% of men. Conclusion: The current study showed a predominance of the Omicron BA.2 variant outcompeting the BA.1 over a period in eastern UP. Most of the cases had a breakthrough infection following the recommended two doses of vaccine with four in five cases being symptomatic. There is a need to further explore the immune evasion properties of the Omicron variant.

Predictors of Free Flap Volume Loss in Nonosseous Reconstruction of Head and Neck Oncologic Defects.

OBJECTIVES: Free tissue reconstruction of the head and neck must be initially overcorrected due to expected postoperative free flap volume loss, which can be accelerated by adjuvant radiation therapy. In this study, we aim to identify patient and treatment-specific factors that may significantly contribute to this phenomenon and translate these characteristics into a predictive model for expected percent free flap volume loss in a given patient. METHODS: Patients with a history of oral cavity and/or oropharyngeal cancer who underwent nonosseous free flap reconstruction were reviewed between January 2009 and November 2018 at a tertiary care center. Demographics/characteristics, total radiation dose, radiation fractionation (RF), and pre/postradiation free flap volume as evaluated by computed tomography imaging were collected. Free flap volume was measured by a fellowship-trained neuroradiologist in all cases. Only patients receiving adjuvant radiotherapy with available pre/postradiation imaging were included. Multivariable linear regression modeling for prediction of free flap volume loss was performed with optimization via stepwise elimination. RESULTS: Thirty patients were included for analysis. Mean flap volume loss was 42.7% ± 17.4%. The model predicted flap volume loss in a significant fashion (P = .004, R2 = 0.49) with a mean magnitude of error of 9.8% ± 7.5%. Age (ß = 0.01, P = .003) and RF (ß = -0.01, P = .009) were individual predictors of flap volume loss. CONCLUSIONS: Our model predicts percent free flap volume loss in a significant fashion. Age and RF are individual predictors of free flap volume loss, the latter being a novel finding that is also modifiable through hyperfractionation radiotherapy schedules.

Colorectal cancer survivorship care plans: Variations in documentation and posttreatment surveillance recommendations.

BACKGROUND: Survivorship care plans (SCP) should outline pertinent information about cancer treatment and follow-up. METHODS: We descriptively analyzed the content of 74 colorectal cancer SCPs completed as part of a randomized, controlled trial of SCPs at an academic and community cancer center. Surveillance recommendations were compared with American Cancer Society, American Society of Clinical Oncology and National Comprehensive Cancer Network guidelines. RESULTS: SCP information provided in >80% of the plans included participant age, cancer diagnosis, details, and side-effects of treatment (surgery, chemotherapy, radiation) and health promotion recommendations. SCP content documented less frequently included predisposing conditions, genetic counseling/testing information and staging. Posttreatment surveillance recommendations were documented in >90% SCPs. For stage 2-3 cancer, rates of guideline concordant recommendations were 100% for colonoscopy surveillance (Year 1 only), 87% for imaging surveillance, 65% for carcinoembryonic antigen surveillance, and 33% for follow-up visits. Excluding colonoscopy, >15 unique recommendations were listed for each modality across stages and sites, with more variation at the academic site. CONCLUSIONS: SCPs consistently recorded information about cancer diagnosis and treatment but omitted critical information about cancer-specific details denoting risk. Surveillance recommendations varied considerably between cancer centers. Future work to improve the consistency of surveillance recommendations documented in SCPs may be needed.

What are survivorship care plans failing to tell men after prostate cancer treatment?

BACKGROUND: Survivorship care plans contain important information for patients and primary care physicians regarding appropriate care for cancer survivors after treatment. We describe the completeness of prostate cancer survivorship care plans and evaluate the concordance of follow-up recommendations with guidelines. METHODS: We analyzed 119 prostate cancer survivorship care plans from one academic and one community cancer center, abstracting demographics, cancer/treatment details, and follow-up recommendations. Follow-up recommendations were compared with the American Cancer Society (ACS), American Society of Clinical Oncology (ASCO), and National Comprehensive Cancer Network (NCCN) guidelines. RESULTS: Content in >90% of plans included cancer TNM stage; prostate-specific antigen (PSA) at diagnosis; radiation treatment details (98% of men received radiation); and PSA monitoring recommendations. Potential treatment-specific side effects were listed for 82% of men who had surgery, 86% who received androgen deprivation therapy (ADT), and 97% who underwent radiation. The presence of posttreatment symptoms was noted in 71% of plans. Regarding surveillance follow-up, all guidelines recommend an annual digital rectal exam (DRE). No plans specified DRE. However, all 71 plans at the community site recommended at least annual follow-up visits with urology, radiation oncology, and primary care. Only 2/48 plans at the academic site specified follow-up visits. All guidelines recommend PSA testing every 6-12 months for 5 years, then annually. For the first 5 years, 90% of plans were guideline-concordant, 8% suggested oversurveillance, and 2% were incomplete. In men receiving ADT, ACS and ASCO recommend bone density imaging and NCCN recommends testosterone levels. Of 77 men on ADT, 1% were recommended bone density imaging and 16% testosterone level testing. CONCLUSIONS: While care plan content is more complete for demographic and treatment summary information, both sites had gaps in reporting posttreatment symptoms and ADT-related testing recommendations. These findings highlight the need to improve the quality of information in care plans, which are important in communicating appropriate follow-up recommendations to patients and primary care physicians.

Functional Hearing Loss and Social Engagement Among Medicare Beneficiaries.

OBJECTIVES: Hearing loss is common in older adults and limits communication. We investigated the independent association between functional hearing loss and social engagement in a nationally representative sample of older adults. METHODS: Using data from the 2015 Medicare Current Beneficiaries Survey, we modeled the cross-sectional association between self-reported hearing ability and limitation in social activity over the past month using multivariable logistic regression. RESULTS: The majority of the study population was female (54.8%) and non-Hispanic white (74.3%). Participants (40.4%) reported "a little trouble" hearing and 7.4% reported "a lot of trouble" hearing. Those who reported any trouble hearing had higher odds of limited social engagement in the past month. After adjustment for demographic, clinical, and functional covariates, those who reported "a lot of trouble" hearing had 37% higher odds of limited social activity in the past month compared to those with normal hearing. DISCUSSION: These results suggest that hearing loss may be an important risk factor for limited social engagement and downstream negative health consequences, independent of other disability and health conditions.

Hearing Loss, Hearing Aid Use, and Depressive Symptoms in Older Adults-Findings from the Atherosclerosis Risk in Communities Neurocognitive Study (ARIC-NCS).

OBJECTIVES: Investigate the cross-sectional association between hearing loss (HL), hearing aid use, and depressive symptoms in community-dwelling older adults. METHOD: The analytic sample consisted of 3,188 participants (age range 71-94 years) in the Atherosclerosis Risk in Communities Neurocognitive Study (ARIC-NCS). Multivariable logistic regression was used to evaluate the association of audiometric hearing status and self-reported hearing aid use with depressive symptoms (11-item Center for Epidemiologic Studies Depression scale). RESULTS: 4.6% of participants had depressive symptoms. Forty percent had mild HL and 27% had moderate or greater HL. In multivariable-adjusted models, mild HL was associated with 1.90 times higher odds (95% confidence interval [CI] 1.20-3.01) and moderate or greater HL with 2.42 times higher odds (95% CI 1.44-4.07) of depressive symptoms compared to normal hearing. Each 10dB increase in HL was associated with 1.30 higher odds of depressive symptoms (95% CI 1.14-1.49). Hearing aid use was not associated with depressive symptoms among those with mild (odds ratio [OR] 0.94, 95% CI 0.35-2.54) or moderate or greater (OR 1.12, 95% CI 0.60-2.11) HL. DISCUSSION: Older adults with HL have higher odds of depressive symptoms compared to adults with normal hearing. Future studies are needed to assess whether hearing care is protective against depressive symptoms in older adults.

Hearing Loss, Loneliness, and Social Isolation: A Systematic Review.

OBJECTIVE: Social isolation and loneliness are associated with increased mortality and higher health care spending in older adults. Hearing loss is a common condition in older adults and impairs communication and social interactions. The objective of this review is to summarize the current state of the literature exploring the association between hearing loss and social isolation and/or loneliness. DATA SOURCES: PubMed, Embase, CINAHL Plus, PsycINFO, and the Cochrane Library. REVIEW METHODS: Articles were screened for inclusion by 2 independent reviewers, with a third reviewer for adjudication. English-language studies of older adults with hearing loss that used a validated measure of social isolation or loneliness were included. A modified Newcastle-Ottawa Scale was used to assess the quality of the studies included in the review. RESULTS: Of the 2495 identified studies, 14 were included in the review. Most of the studies (12/14) were cross-sectional. Despite the heterogeneity of assessment methods for hearing status (self-report or objective audiometry), loneliness, and social isolation, most multivariable-adjusted studies found that hearing loss was associated with higher risk of loneliness and social isolation. Several studies found an effect modification of gender such that among women, hearing loss was more strongly associated with loneliness and social isolation than among men. CONCLUSIONS: Our findings that hearing loss is associated with loneliness and social isolation have important implications for the cognitive and psychosocial health of older adults. Future studies should investigate whether treating hearing loss can decrease loneliness and social isolation in older adults.

Molecular modeling, simulation and principal component analysis of binding of resveratrol and its analogues with DNA.

Structure-based drug designing has become a significant subject of research, and several clinically promising DNA binding compounds were evolved using this technique. The interaction of an octamer DNA sequence d(CCAATTGG)2 with a natural stilbene, resveratrol and its analogues have been studied using molecular docking method. Out of the ten compounds studied, seven compounds were found to bind to the minor groove of AATT segment of the sequence. Pterostilbene, a natural analogue of resveratrol, showed the lowest binding energy. Rhaponticin, a natural analogue of resveratrol and digalloylresveratrol, a synthetic ester of resveratrol bind to the major groove of the AATT segment while dihydroresveratrol binds to the minor groove of GC terminal base pair. ADMET (Absorption, distribution, metabolism, excretion and toxicity) study showed that all compounds obey Lipinski rule and are accepted as orally active drugs based on different physicochemical descriptors. Molecular dynamics simulations were performed for the complex with lowest binding energy and trajectory analysis were performed. Principal component analysis has been performed to underline the prominent motions in alone DNA and when it is bound to pterostilbene. AbbreviationsADMETAbsorption, distribution, metabolism, excretion and toxicityDIGDigalloyl resveratrolDNADeoxyribonucleic acidELElectrostatic energyENPOLARNonpolar solvation energyESURFSurface areaGBGeneralized BornHBAHydrogen bond acceptorsHBDHydrogen bond donorsLGALamarckian genetic algorithmMDMolecular dynamicsPBPoisson-BoltzmannPCAPrincipal component analysisPTPterostilbeneRMSDRoot mean square deviationSASimulated annealingTLX3T-cell leukemia homeobox 3VDWvan der WaalsCommunicated by Ramaswamy H. Sarma.

Breast cancer survivorship care plans: what are they covering and how well do they align with national guidelines?

PURPOSE: Survivorship care plans (SCPs) provide key information about cancer treatment history and follow-up recommendations. We describe the completeness of breast cancer SCPs and evaluate guideline concordance of follow-up recommendations. METHODS: We analyzed 149 breast cancer SCPs from two sites, abstracting demographics, cancer/treatment details, surveillance plans, and health promotion advice. SCP recommendations and provided information were compared to American Cancer Society/American Society of Clinical Oncology and National Comprehensive Cancer Network guidelines. RESULTS: SCP information provided in > 90% of the plans included patient age; relevant providers; cancer stage; treatment details; and physical exam, mammogram, and health promotion recommendations. SCP components completed less frequently included post-treatment symptoms/side effects (67%). All SCPs at the community site were uniform but had the potential for oversurveillance if visits occurred every 3 months in years 1-2 or every 6 months in years 3-5 with multiple cancer providers. The academic site recommended three predominant patterns of follow-up: (1) primary care provider every 6-12 months; (2) cancer team every 3-6 months (year 1), every 6-12 months (years 4-5); and (3) alternating oncology providers every 3-6 months (years 1-2) then every 6 months. Compared to guidelines, these patterns recommend under- and oversurveillance at various times. Mammography recommendations showed guideline concordance (annual) for 84%, oversurveillance for 10%, and were incomplete for 6%. SCPs of only 12/79 (15%) women on aromatase inhibitors recommended guideline-concordant bone density testing. CONCLUSIONS: SCP content is more complete for demographic and treatment summary information but has follow-up recommendation gaps. Efforts to improve follow-up recommendations are needed.

Association between patient-reported outcomes and objective disease indices in people with NF2.

OBJECTIVE: The association between patient-reported outcomes and currently used clinical trial endpoints, including total vestibular schwannoma (VS) volume and word recognition score (WRS) in neurofibromatosis type 2 (NF2), is not known. METHODS: A prospective observational study enrolling adult patients with NF2 was conducted at a single specialty center. Measures included: NF2 impact on quality of life (NFTI-QOL), short form (SF)-36; total VS volume, WRS; provider- and patient-reported disease severity (ProvSev, PatSev) measured with an institutionally derived multi-item (e.g., symptom burden, age-of-onset, and fatality-risk) and single-item Likert (mild, moderate, severe) scale. RESULTS: Fifty-one patients were enrolled between June 2014 and August 2017. Mean age was 42.1 ± 18.2 years and 37.3% patients were male. Mean WRS was 74.4 ± 37.3%; mean total VS volume was 4.2 ± 5.2 cc. Additional lesions were common including meningioma (79.2%) and spinal ependymoma (39.6%). Mean NFTI-QOL score was 7.6 ± 4.9 and correlated with responses on the SF-36. NFTI-QOL also correlated well with PatSev (r = 0.63, p < 0.001) and both multi- and single-item ProvSev (r = 0.62, p < 0.001; r = 0.52, p < 0.001, respectively). A weak correlation was observed between NFTI-QOL and WRS (r = -0.34, p = 0.0156). There was no correlation with VS volume (r = 0.23, p = 0.15). CONCLUSIONS: The NFTI-QOL correlated well with multiple measures of disease severity but not commonly accepted endpoints for NF2 clinical trials including total VS volume in this US cohort of patients with NF2. This suggests that the NFTI-QOL captures components of the patient experience not sufficiently represented by objective measures of disease and underscores the important and complementary role of patient-focused measures in therapeutic outcome assessment in people with NF2.

Impact of Hearing Loss on Patient-Provider Communication Among Hospitalized Patients: A Systematic Review.

Age-related hearing loss is a highly prevalent chronic condition in older adults, but hearing loss is rarely accounted for in patient-provider communication studies. This systematic review synthesizes current evidence on the impact of age-related hearing loss on patient-provider communication in hospitalized older adults. Five databases were queried to identify original research that examined patient-provider communication in older adults with hearing loss in an inpatient setting. Of 1053 studies, 13 were included in the final review. All studies reported an adverse effect of hearing loss on patient-provider communication. Among studies that evaluated an intervention to improve communication in older adults with hearing loss, simple interventions such as low-cost voice amplifiers were found to improve communication. An understanding of the effect of hearing loss on patient-provider communication and strategies to mitigate the impact are needed in order to provide safe, quality, patient-centered care to older adults with hearing loss.