Domestic and International Cosmetic Tourism Complications Presenting to a U.S. Tertiary Hospital.

BACKGROUND: Cosmetic surgery tourism has become a significant global industry. Oftentimes, patients who develop postoperative complications present for care in their home U.S. state. OBJECTIVES: This study evaluated patients who either traveled abroad or to other states within the United States for cosmetic surgeries and returned with complications treated in the authors' center. We sought to compare rates of complications between patients that underwent cosmetic surgery internationally and domestically. METHODS: This retrospective cross-sectional study reviewed patients who presented from June 2014 to June 2022 with concerns related to cosmetic surgeries performed in another state or abroad. Binary logistic regressions were performed to assess differences in outcomes between domestic and international cases, including complications, interventions, and admissions. RESULTS: One-hundred twenty-three patients (97.6% female, me an age 34.0 ± 8.7 years, range 16-62 years) comprised 159 emergency department consultations. The most common procedures included abdominoplasty (n=72) and liposuction (n=56). Complications included wound dehiscence (n=39), infection (n=38), and seroma (n=34). Over one-half of patients required intervention. Twenty-nine patients (23.6%) required hospital admission. On multivariate regression analyses, incidence of seroma (p=0.025) and oral (p=0.036) and intravenous antibiotic prescriptions (p=0.045) were significantly greater among the international cohort compared to domestic, whereas all other complication variables were non-significant. There were no other significant differences in operative interventions or hospital admissions between international and domestic cohorts. CONCLUSIONS: Compared to domestic tourism cases, international tourism cases were associated with significantly higher rates of seroma formation and antibiotic use. There were no significant differences otherwise in overall complications including infections, operative interventions, or hospital admissions.

Anterior and superior plate positions in diaphyseal clavicle fractures produce similar patient outcomes.

PURPOSE: While diaphyseal clavicle fractures can be treated with plate fixation on either the superior or anteroinferior aspect of the clavicle, the optimal plate position remains controversial. The purpose of this study was to determine if anteroinferior vs. superior plating for clavicle fracture fixation leads to better patient outcomes. METHODS: A retrospective review of patients who sustained clavicle fractures (OTA/AO 15.2) treated with superior or anteroinferior plating at a tertiary Level I trauma center from 2015 to 2021 was performed. The clinical outcomes of clavicle fractures were compared between groups treated with an anterior versus a superior approach via Mann-Whitney U and Chi-squared tests as appropriate to evaluate for differences in outcomes between the two plate positions. RESULTS: A total of 315 diaphyseal clavicle fractures were identified. One hundred and forty patients were excluded due to inadequate follow-up. Of the remaining 175 patients, 25 were treated with an anteroinferior approach (14%) and 150 were treated with a superior approach (86%). There were no differences in age, BMI, tobacco use, or substance use between the two groups (p > 0.05 for all). On univariate analysis, there was no difference in rate of union (p = 0.60), nerve injury (p = 0.60), infection (p = 1.0), implant-related irritation (p = 0.42), implant removal (p = 0.26), or revision (p = 1.0) based on approach. Contoured plates had an association with risk of nerve injury (p = 0.04). CONCLUSION: There are no differences in union, nerve injury, infection, symptomatic implant, or revision rate between anteroinferior and superior clavicle approaches. Plate positioning during diaphyseal clavicle fracture fixation can reasonably be dictated based on surgeon preference and ideal reduction quality.

Clinically Significant Prostate Cancer Detection After a Negative Prebiopsy MRI Examination: Comparison of Biparametric Versus Multiparametric MRI.

BACKGROUND. The frequency of clinically significant prostate cancer (csPCa) following negative biparametric MRI (bpMRI) and multiparametric MRI (mpMRI) has not been well investigated in direct comparative studies. OBJECTIVE. The purposes of this study were to compare the frequency of csPCa after negative prebiopsy bpMRI and mpMRI and to evaluate factors predictive of csPCa in the two cohorts. METHODS. This retrospective study included 232 men (mean age, 64.5 years) with negative bpMRI from August 2017 to March 2020 and 193 men (mean age, 69.0 years) with negative mpMRI from January 2018 to December 2018. PI-RADS category 1 or 2 was defined as negative. The study institution offered bpMRI as a low-cost self-pay option for patients without insurer coverage of prebiospy mpMRI. Patient characteristics and subsequent biopsy results were recorded. CsPCa was defined as Gleason score of 3 + 4 or greater. Multivariable regression analyses were performed to identify independent predictors of csPCa. The AUC of PSA density (PSAD) for csPCA was computed, and the diagnostic performance of PSAD was assessed at a clinically established threshold of 0.15 ng/mL2. RESULTS. Systematic biopsy was performed after negative bpMRI for 41.4% (96/232) of patients and after negative mpMRI for 30.5% (59/193) (p = .02). Among those undergoing biopsy, csPCa was present in 15.6% (15/96) in the bpMRI cohort versus 13.6% (8/59) in the mpMRI cohort (p = .69). The NPV for csPCa was 84% (81/96) for bpMRI and 86% (51/59) for mpMRI. In multivariable analyses, independent predictors of csPCa included smaller prostate volume (OR, 0.27; p < .001) and greater PSAD (OR, 3.09; p < .001). In multivariable models, bpMRI (compared with mpMRI) was not independently predictive of csPCa (p > .05). PSAD had an AUC for csPCa of 0.71 (95% CI, 0.56-0.87) in the bpMRI cohort versus 0.68 (95% CI, 0.42-0.93) in the mpMRI cohort. For detecting csPCa, a PSAD threshold of 0.15 ng/mL2 had NPV of 90% and PPV of 28%, in the bpMRI cohort versus NPV of 92% and PPV of 44% in the mpMRI cohort. CONCLUSION. The frequencies of csPCa were not significantly different at systematic biopsy performed after negative bpMRI and mpMRI examinations. PSAD had similar diagnostic utility for csPCa in the two cohorts. CLINICAL IMPACT. Either bpMRI or mpMRI, in combination with PSAD measurement, can help avoid negative prostate biopsies.

Clustering patterns of type-type combination in multiple genotypes infections of human papillomavirus in cervical adenocarcinoma.

Coinfections with multiple types of human papillomavirus (HPV) occur in cervical adenocarcinoma (ADC). However, it remains unclear the clustering patterns of multiple types in HPV coinfections and relevant factors in ADC. A total of 718 paraffin-embedded ADC specimens were collected in China and tested for HPV genotypes using SPF10-INNO-LIPA. The prevalence of HPV coinfections and clustering patterns by geographical regions, histological subtypes and ages were assessed. Type-specific attribution of HPV to ADC adjusted by HPV coinfections were calculated. The prevalence of HPV coinfections was found to be 8.4% in ADC cases with slight variation by geographic regions between 2.2% and 12.5%. The 88.3% of all HPV multiple infections in ADC were two types of HPV coinfections with predominant combination of HPV 16 and HPV 18. The attribution to ADC was 88.0% for HPV 16/18 targeted by bivalent and quadrivalent vaccine and 96.8% for HPV 16/18/31/33/45/52/58 targeted by nonavalent vaccine. Clustering patterns of multiple types were related with histological categories and age at diagnosis. In conclusion, HPV coinfections are uncommonly prevalent in ADC cases with slight variation by geographic regions and distinct clustering patterns of multiple types by histological subtypes and ages at diagnosis. The high attribution of carcinogenic HPV types to ADC predicts potential protection of HPV vaccine against ADC.

Clinical Performance of Human Papillomavirus Testing and Visual Inspection With Acetic Acid in Primary, Combination, and Sequential Cervical Cancer Screening in China.

BACKGROUND: World Health Organization guidelines recommend screening with human papillomavirus (HPV) testing followed by either treatment of all HPV-positives, or by visual inspection (VIA) for triage to treatment, citing insufficient evidence to recommend either strategy over the other. METHODS: We assessed VIA and HPV testing individually, in combination (HPV-VIA cotesting), and as triage models. Three thousand women were screened in Inner Mongolia, China, concurrently with HPV testing and VIA in a real population setting. Screen-positive women underwent colposcopy, and biopsy, if indicated. Accuracy of screening algorithms for cervical intraepithelial neoplasia grade 2 or higher (CIN-2+) was calculated after controlling for verification bias. HPV testing followed by VIA triage for CIN-2+ detection was compared with Hybrid Capture 2 viral loads triage, measured in relative light units/cutoff. RESULTS: CIN-2+ prevalence was 1.0%. Corrected sensitivity, false negative rate, and specificity for CIN-2+, respectively, for primary HPV testing were 89.7%, 10.3%, and 83.3%; 44.8%, 55.2%, and 92·3% for VIA; 93.1%, 6.9%, and 80.2% for HPV-VIA cotesting; and 41.4%, 58.6, and 95.4% for HPV with VIA triage scenarios. Using relative light units/cutoff of 5 or greater to triage HPV-positive women had twice the sensitivity as VIA triage, with comparable specificity for CIN-2+. CONCLUSIONS: When VIA performs relatively poorly and HPV testing is available, adding VIA to sequential (ie, HPV followed by VIA triage) or primary (HPV-VIA cotesting) screening does not significantly improve CIN-2+ detection beyond primary HPV screening alone. Sequential screening (ie, HPV followed by VIA triage) reduces sensitivity too low for population-based screening programs. The HPV viral loads could offer an alternative low-resource country triage strategy.

Human papillomavirus viral load as a useful triage tool for non-16/18 high-risk human papillomavirus positive women: A prospective screening cohort study.

OBJECTIVE: ASCCP cervical cancer screening guidelines recommend triaging high-risk human papillomavirus (hrHPV) positive women with cytology and genotyping, but cytology is often unavailable in resource-limited areas. We compared the long-term risk of cervical cancer and precancers among type-specific hrHPV-positive women triaged by viral load to cytology and visual inspection with acetic acid (VIA). METHODS: A cohort of 1742 Chinese women was screened with cytology, VIA, and Hybrid Capture 2 (HC2) test and followed for ten years. All HC2-positive samples were genotyped. Viral load was measured by HC2 relative light units/cutoff (RLU/CO). Ten-year cumulative incidence rate (CIR) of cervical intraepithelial neoplasia grade 2 or worse (CIN2+) for type-specific hrHPV viral load was estimated using Kaplan-Meier methods. RESULTS: Baseline hrHPV viral load stratified by specific genotypes was positively correlated with prevalent cytological lesions. Ten-year CIR of CIN2+ was associated with cytological lesions and viral load. Among HPV 16/18-positive women, ten-year CIR of CIN2+ was high, even with normal cytology (15.3%), normal VIA (32.4%), viral load with RLU/CO<10 (23.6%) or RLU/CO<100 (33.8%). Among non-16/18 hrHPV positive women, ten-year CIR of CIN2+ was significantly stratified by cytology grade of atypical squamous cell of undetermined significance or higher (2.0% VS. 34.6%), viral load cutoffs at 10 RLU/CO (5.1% VS. 27.2%), at 100 RLU/CO (11.0% VS. 35.5%), but not by VIA (19.1% VS. 19.0%). CONCLUSIONS: Our findings support the guidelines in referring all HPV16/18 positive women to colposcopy and suggest triaging non-16/18 hrHPV positive women using viral loads in resource-limited areas where cytology screening was inaccessible.

Bilateral Sixth Nerve Palsy and Nasal Voice in Two Sisters as a Variant of Guillan-Barré Syndrome.

A 6-year-old girl with acute pharyngitis presented with complaints of hypernasal speech and double vision. Examination revealed a bilateral abduction deficit associated with soft palate palsy causing rhinolalia aperta. Cerebrospinal fluid analysis showed albuminocytologic dissociation. Her sister also suffered from the same disorder, albeit milder, 1 month before. After treatment with intravenous immunoglobulin and steroids, the patient made a full recovery. After the case report, a brief discussion of Miller Fisher syndrome, Guillan-Barré syndrome, and their variants is made. This case highlights that bilateral sixth nerve palsy and rhinolalia aperta in the absence of ataxia should still raise suspicion for these autoimmune conditions that may rarely and atypically present in siblings.

From A to Z(OOR): The Clinical Spectrum of Acute Zonal Occult Outer Retinopathy.

Acute idiopathic blind spot enlargement (AIBSE) is often caused by Acute Zonal Occult Outer Retinopathy (AZOOR), an outer retinal disease. We report two illustrative cases of AZOOR. The first one was a 21-year-old white female who presented with a scotoma and "shimmering lights" in her left eye. In the second case, a 73-year-old white female was referred for evaluation of a "bitemporal hemianopsia" that started years prior, with no clinical significant photopsias. To our knowledge, case two is the longest documented duration of bilateral, progressive, and chronic, idiopathic, enlargement of the blind spot (CIBSE) documented in the English language ophthalmic literature.

Evaluation of menopausal status among breast cancer patients with chemotherapy-induced amenorrhea.

OBJECTIVE: In patients with chemotherapy-induced amenorrhea (CIA), the menopausal status is ambiguous and difficult to evaluate. This study aimed to establish a discriminative model to predict and classify the menopausal status of breast cancer patients with CIA. METHODS: This is a single center hospital-based study from 2013 to 2016. The menopausal age distribution and accumulated incidence rate of CIA are described. Multivariate models were adjusted for established and potential confounding factors including age, serum concentration of estradiol (E2) and follicle-stimulating hormone (FSH), feeding, pregnancy, parity, abortions, and body mass index (BMI). The odds ratio (OR) and 95% confidence interval (95% CI) of different risk factors were estimated. RESULTS: A total of 1,796 breast cancer patients were included in this study, among whom, 1,175 (65.42%) were premenopausal patients and 621 (34.58%) were post-menopause patients. Five hundred and fifty patients were included in CIA analysis, and a cumulative CIA rate of 81.64% was found in them. Age (OR: 1.856, 95% CI: 1.732-1.990), serum concentration of E2 (OR: 0.976, 95% CI: 0.972-0.980) and FSH (OR: 1.060, 95% CI: 1.053-1.066), and menarche age (OR: 1.074, 95% CI: 1.009-1.144) were found to be associated with the patients' menopausal status. According to multivariate analysis, the discriminative model to predict the menopausal status is Logit (P)=-28.396+0.536Age-0.014E2+0.031FSH. The sensitivities for this model were higher than 85%, and its specificities were higher than 89%. CONCLUSIONS: The discriminative model obtained from this study for predicting menstrual state is important for premenopausal patients with CIA. This model has high specificity and sensitivity and should be prudently used.

Paraspinal neurofibromas and hypertrophic neuropathy in Noonan syndrome with multiple lentigines.

BACKGROUND: Noonan syndrome with multiple lentigines (NSML), formerly known as LEOPARD syndrome, is an autosomal-dominant disorder characterised by lentigines, EKG abnormalities, ocular hypertelorism, pulmonic stenosis, abnormal genitalia, growth retardation and deafness. There is significant clinical overlap between NSML and other disorders that result from dysregulated rat sarcoma/mitogen-activated protein kinase pathway (RASopathies). Except for neurofibromatosis type 1, other RASopathies are not known to be typically associated with neurogenic tumours. METHODS AND RESULTS: We evaluated patients from three families with pigmentary skin lesions, progressive neuropathy, enlarged nerves, massive burden of paraspinal tumours (neurofibroma was confirmed in one patient) and a clinical diagnosis of NSML. All patients had a mutation in the protein tyrosine phosphatase catalytic domain of the PTPN11 gene; two unrelated patients had the p.Thr468Met mutation, while the family consisting of two affected individuals harboured the p.Thr279Cys mutation. Molecular analysis performed on hypertrophic nerve tissue did not disclose a second somatic hit in NF1, PTPN11, NF2 or SMARCB1 genes. CONCLUSIONS: Neurogenic tumours and hypertrophic neuropathy are unusual complications of NSML and may be an under-recognised manifestation that would warrant surveillance. Our observation may also have implications for other disorders caused by RAS-pathway dysregulation.

Accuracy of triage strategies for human papillomavirus DNA-positive women in low-resource settings: A cross-sectional study in China.

OBJECTIVE: CareHPV is a human papillomavirus (HPV) DNA test for low-resource settings (LRS). This study assesses optimum triage strategies for careHPV-positive women in LRS. METHODS: A total of 2,530 Chinese women were concurrently screened for cervical cancer with visual inspection with acetic acid (VIA), liquid-based cytology and HPV testing by physician- and self-collected careHPV, and physician-collected Hybrid Capture 2 (HC2). Screen-positive women were referred to colposcopy with biopsy and endocervical curettage as necessary. HPV-positivity was defined as ≥1.0 relative light units/cutoff (RLU/CO) for both careHPV and HC2. Primary physician-HC2, physician-careHPV and self-careHPV and in sequential screening with cytology, VIA, or increased HPV test-positivity performance, stratified by age, were assessed for cervical intraepithelial neoplasia (CIN) grade 2/3 or worse (CIN2/3+) detection. RESULTS: The sensitivities and specificities of primary HPV testing for CIN2+ were: 83.8%, 88.1% for physician-careHPV; 72.1%, 88.2% for self-careHPV; and 97.1%, 86.0% for HC2. Physician-careHPV test-positive women with VIA triage had a sensitivity of 30.9% for CIN2+ versus 80.9% with cytology triage. Self-careHPV test-positive women with VIA triage was 26.5% versus 66.2% with cytology triage. The sensitivity of HC2 test-positive women with VIA triage was 38.2% versus 92.6% with cytology triage. The sensitivity of physician-careHPV testing for CIN2+ decreased from 83.8% at ≥1.0 RLU/CO to 72.1% at ≥10.00 RLU/CO, while the sensitivity of self-careHPV testing decreased from 72.1% at ≥1.0 RLU/CO to 32.4% at ≥10.00 RLU/CO; similar trends were seen with age-stratification. CONCLUSIONS: VIA and cytology triage improved specificity for CIN2/3 than no triage. Sensitivity with VIA triage was unsuitable for a mass-screening program. VIA provider training might improve this strategy. Cytology triage could be feasible where a high-quality cytology program exists. Triage of HPV test-positive women by increased test positivity cutoff adds another LRS triage option.

Intracerebral coinfection with Burkholderia pseudomallei and Cryptococcus neoformans in a patient with systemic lupus erythematosus.

Infections are a serious complication in patients with systemic lupus erythematosus (SLE), and are an important cause of morbidity and mortality. SLE patients are particularly susceptible to infection due to immune suppression from underlying disease or treatment. Most infections are due to common bacterial organisms. Clinicians also need to be aware of the possibility of polymicrobial infections as these may cause diagnostic delay and affect outcomes. We report the case of an intra-cerebral coinfection with Burkholderia pseudomallei and Cryptococcus neoformans in a 34-year-old woman with SLE. The diagnosis in this case was delayed since coinfection was not suspected.

A scoping review of vasculitis as an immune-related adverse event from checkpoint inhibitor therapy of cancer: Unraveling the complexities at the intersection of immunology and vascular pathology.

BACKGROUND/PURPOSE: Vasculitis as an immune-related adverse event (irAE) from checkpoint inhibitor therapy (ICI) to treat cancer is a rare clinical event, and little is known regarding its nosology, clinical manifestations, or response to treatment and outcomes. METHODS: To address these gaps, we used the Preferred Reporting Items for Systemic Reviews and Meta-Analyses Extension for Scoping Reviews (PRISMA-ScR) framework to further define this complication. Two independent PUBMED searches in September and November of 2022 revealed 127 publications with 37 excluded from title by relevance, 43 excluded by article type, and 23 excluded due to lack of biopsy results, or biopsy negative for vasculitis. Twenty-nine documented cases from 24 publications were included for final analysis. Basic demographics, ICI details, timing of onset of vasculitis symptoms, irAE treatment and outcomes were collected. The vasculitides were classified using 2022 ACR/EULAR Vasculitis Classification Criteria as well as 2012 Revised Chapel-Hill Nomenclature. Adaptations from Naidoo et al. 2023 [1] consensus definitions for irAEs were used and efforts were made to classify steroid-responsive versus unresponsive irAEs. RESULTS: Of the 29 cases reviewed, the average age of patients was 62.1 ± 11.0, composed of 58.6 % (n = 17) male and 41.3 % (n = 12) female. Prominent cancer types were lung cancer (41.4 %; n = 12), melanoma (41.4 %; n = 12), and renal cancer (10.3 %; n = 3), with majority being stage 4 (75.9 %, n = 22) and stage 3 (10.3 %, n = 3). Only 8 cases met the ACR/EULAR criteria, and by Chapel-Hill Nomenclature, approximately a third were small-vessel vasculitis (31.0 %; n = 9) with n = 4 positive for ANCA. Most biopsies were taken from the skin (37.9 %, n = 11) and kidney (24.1 %, n = 7). Patients were either treated with single (65.5 %, n = 19), dual (17.2 %; n = 5), or sequential (17.2 %; n = 5) ICI regimen which included anti-PD-1 therapy in all but one case, with mean of 8.7 ± 10.5 cycles received. Mean time to onset of symptoms from start of ICI was 7.2 ± 7.8 months, with 55.2 % occurring >3 months since the initial immunotherapy. Vasculitis treatment included glucocorticoids in 96 % of cases and immunotherapy was often discontinued (44.8 %; n = 13). Clinical improvement of irAE was documented in 86.2 % (n = 25). Data were missing in terms of fate of ICI (34.5 %; n = 10) and tumor outcomes (41.4 %; n = 12). Cancer progressed in 20.7 % (n = 6), stable in 34.5 % (n = 10) cases, and 6 patients died of all-causes. CONCLUSION: Vasculitis as an irAE appears clinically heterogeneous and rare. Among reported cases with adequate documentation, vasculitis is of delayed onset following the initiation of immunotherapy. Outcomes of ICI-vasculitis were generally favorable, responding to glucocorticoids and immunotherapy withdrawal. There is an urgent need for more standardized reporting of rare irAEs such as vasculitis to clarify clinical risks, classification, relationship to immunotherapy and outcomes.

Differences in self-reported disruptions in mental health treatment during COVID-19 in a national household sample: impact of severity of functional impairment.

Objective: This report uses data from Mental Disorders Prevalence Study (MDPS), a large epidemiologic study that provided national prevalence estimates of seven mental disorders based on the Structured Clinical Interview for DSM-5 (SCID), to assess the odds of treatment disruption during COVID for SMI and non-SMI groups. Methods: This cross-sectional study conducted from 2020 to 2022 included 2,810 household participants with any lifetime mental health treatment. Weighted logistic regressions estimated the odds of reporting disruptions in access to mental health care or psychotropic prescriptions due to COVID. SMI was broadly defined as having an MDP diagnosis and serious functional impairment (GAF ≤50, a validated and widely used cutoff). Non-SMI groups were a mental diagnosis without serious impairment (MDPS diagnosis, GAF >50) and any lifetime treatment and no serious impairment (no MDPS diagnosis, GAF >50). Results: The SMI and mental disorder without serious impairment groups had approximately 6.4- and 2.4- greater odds, respectively, of reporting inability to access mental health care and 4- and 3- greater odds, respectively, of having prescriptions delayed, relative to the group with any lifetime treatment. Among those with serious mental illness, having Medicare insurance increased the odds of reporting inability to access mental health care. Conclusions: Individuals with SMI were much more likely to experience treatment disruptions throughout the pandemic than non-SMI groups.

Neoadjuvant Dual Checkpoint Inhibitors vs Anti-PD1 Therapy in High-Risk Resectable Melanoma: A Pooled Analysis.

Importance: Despite the clear potential benefits of neoadjuvant therapy, the optimal neoadjuvant regimen for patients with high-risk resectable melanoma (HRRM) is not known. Objective: To compare the safety and efficacy of dual checkpoint inhibitors with anti-programmed cell death protein-1 (anti-PD1) therapy in a neoadjuvant setting among patients with HRRM. Design, Setting, and Participants: In this pooled analysis of clinical trials, studies were selected provided they investigated immune checkpoint inhibitor treatment, were published between January 2018 and March 2023, and were phase 1, 2, or 3 clinical trials. Participant data included in the analysis were derived from trials evaluating the efficacy and safety of anti-PD1 monotherapy and the combination of anti-cytotoxic T lymphocyte-associated protein-4 with anti-PD1 in the neoadjuvant setting, specifically among patients with HRRM. Interventions: Patients were treated with either anti-PD1 monotherapy; dual checkpoint inhibition (DCPI) with a conventional dose of 3-mg/kg ipilimumab and 1-mg/kg nivolumab; or DCPI with an alternative-dose regimen of 1-mg/kg ipilimumab and 3-mg/kg nivolumab. Main Outcomes and Measures: The main outcomes were radiologic complete response (rCR), radiologic overall objective response (rOOR), and radiologic progressive disease. Also, pathologic complete response (pCR), the proportion of patients undergoing surgical resection, and occurrence of grade 3 or 4 immune-related adverse events (irAEs) were considered. Results: Among 573 patients enrolled in 6 clinical trials, neoadjuvant therapy with DCPI was associated with higher odds of achieving pCR compared with anti-PD1 monotherapy (odds ratio [OR], 3.16; P < .001). DCPI was associated with higher odds of grade 3 or 4 irAEs compared with anti-PD1 monotherapy (OR, 3.75; P < .001). When comparing the alternative-dose ipilimumab and nivolumab (IPI-NIVO) regimen with conventional-dose IPI-NIVO, no statistically significant difference in rCR, rOOR, radiologic progressive disease, or pCR was noted. However, the conventional-dose IPI-NIVO regimen was associated with increased grade 3 or 4 irAEs (OR, 4.76; P < .001). Conventional-dose IPI-NIVO was associated with greater odds of achieving improved rOOR (OR, 1.95; P = .046) and pCR (OR, 2.99; P < .001) compared with anti-PD1 monotherapy. The alternative dose of IPI-NIVO also was associated with higher odds of achieving rCR (OR, 2.55; P = .03) and pCR (OR, 3.87; P < .001) compared with anti-PD1 monotherapy. The risk for grade 3 or 4 irAEs is higher with both the conventional-dose (OR, 9.59; P < .001) and alternative-dose IPI-NIVO regimens (OR, 2.02; P = .02) compared with anti-PD1 monotherapy. Conclusion and Relevance: In this pooled analysis of 6 clinical trials, although DCPI was associated with increased likelihood of achieving pathological and radiologic responses, the associated risk for grade 3 or 4 irAEs was significantly lower with anti-PD1 monotherapy in the neoadjuvant setting for HRRM. Additionally, compared with alternative-dose IPI-NIVO, the conventional dose of IPI-NIVO was associated with increased risk for grade 3 or 4 irAEs, with no significant distinctions in radiologic or pathologic efficacy.

Metabolic regulation, mitochondria and the life-prolonging effect of rapamycin: a mini-review.

The fungicide rapamycin increases lifespan in eukaryotes by interfering with the activity of a serine/threonine kinase called TOR (target of rapamycin). TOR complex 1 (TORC1) is an essential integrator of cellular nutrient cues, growth signals and cellular metabolism. Here, we review major components of TORC1, its downstream effectors and lifespan studies in various organisms involving these signaling components. In particular, we focus on the role of rapamycin in mitochondrial biogenesis, in metabolic regulation and in the control of reactive oxygen species production.

An exploratory study of pregnant women's knowledge of child oral health care in New Zealand.

BACKGROUND: To be maximally effective, oral health preventive strategies should start at birth. There appear to be few reports on pregnant women's knowledge of oral health care for their developing children. OBJECTIVES: This exploratory study assessed Dunedin expectant mothers' knowledge of the oral health care of their future children. METHODS: A questionnaire was developed to assess expectant mothers' knowledge of child oral health and appropriate prevention strategies. Three public Lead Maternity Carer (LMC) organisations and 30 private individual LMCs were asked to distribute the questionnaire to their clients attending appointments during a one-month period. Questions focused on the mother's knowledge of oral health practices for their future children, including oral hygiene and access to dental care. RESULTS: Fewer than half of the participants thought they had enough information about their child's oral health needs. One-quarter thought that toothbrushing should not start until after two years of age. The majority thought their child should not be seen by a dental professional until this age, while one-fifth did not think their child should be seen until four years old. Poorer child oral health knowledge was found in first-time mothers, younger women, those from low-SES groups, and those who were not New Zealand (NZ) Europeans. CONCLUSIONS: A substantial number of participants were unaware of how to provide appropriate oral health care for their children despite the available information. This lack of awareness needs to be taken into account when designing oral health promotion strategies for parents of very young children.