Cleft Lip Scar Appearance is Associated With Speech Outcomes After Primary Palatoplasty.

OBJECTIVE: This study aims to investigate the correlation between the quality of cleft lip scar and velopharyngeal insufficiency (VPI). METHODS: Clinical photographs from 56 patients with repaired cleft lip and palate (CLP) were collected and anonymized by cropping the image to the region of interest around the lip and nose. A survey displaying each cleft lip scar image with five associated scar quality features, including scar color, thickness, width, lip shortening, and overall appearance, was distributed. Surveys were distributed using Amazon Mechanical Turk (MTurk), an online crowdsourcing platform, to obtain ratings from 330 laypeople. The same surveys were also distributed to 45 medical students. MAIN OUTCOME MEASURE: Hypernasality was used as the primary speech outcome measure. Ordinal logistic regression was used to compare the ratings for each of the five scar quality categories with the patients' CAPS-A-AM hypernasality rating for both MTurk and medical student raters. Significance was set at α = 0.05. RESULTS: For medical student ratings', ordinal logistic regression showed a statistically significant relationship between lip shortening (P=0.019) and overall appearance (P=0.044) with CAPS-A-AM hypernasality score, whereas the other scar categories showed no significant association. There was no statistically significant relationship between MTurk ratings and hypernasality for any of the scar categories. CONCLUSIONS: The association found between lip shortening and overall scar appearance, thought by the authors to indicate scar contracture, and hypernasality, an indicator of VPI severity, provides an interesting insight into how to potentially identify patients who may be at increased risk for developing VPI.

Fractionated photoimmunotherapy stimulates an anti-tumour immune response: an integrated mathematical and in vitro study.

BACKGROUND: Advanced epithelial ovarian cancer (EOC) has high recurrence rates due to disseminated initial disease presentation. Cytotoxic phototherapies, such as photodynamic therapy (PDT) and photoimmunotherapy (PIT, cell-targeted PDT), have the potential to treat disseminated malignancies due to safe intraperitoneal delivery. METHODS: We use in vitro measurements of EOC tumour cell and T cell responses to chemotherapy, PDT, and epidermal growth factor receptor targeted PIT as inputs to a mathematical model of non-linear tumour and immune effector cell interaction. The model outputs were used to calculate how photoimmunotherapy could be utilised for tumour control. RESULTS: In vitro measurements of PIT dose responses revealed that although low light doses (<10 J/cm2) lead to limited tumour cell killing they also increased proliferation of anti-tumour immune effector cells. Model simulations demonstrated that breaking up a larger light dose into multiple lower dose fractions (vis-à-vis fractionated radiotherapy) could be utilised to effect tumour control via stimulation of an anti-tumour immune response. CONCLUSIONS: There is promise for applying fractionated PIT in the setting of EOC. However, recommending specific fractionated PIT dosimetry and timing will require appropriate model calibration on tumour-immune interaction data in human patients and subsequent validation of model predictions in prospective clinical trials.

PpIX-enabled fluorescence-based detection and photodynamic priming of platinum-resistant ovarian cancer cells under fluid shear stress.

Over 75% percent of ovarian cancer patients are diagnosed with advanced-stage disease characterized by unresectable intraperitoneal dissemination and the presence of ascites, or excessive fluid build-up within the abdomen. Conventional treatments include cytoreductive surgery followed by multi-line platinum and taxane chemotherapy regimens. Despite an initial response to treatment, over 75% of patients with advanced-stage ovarian cancer will relapse and succumb to platinum-resistant disease. Recent evidence suggests that fluid shear stress (FSS), which results from the movement of fluid such as ascites, induces epithelial-to-mesenchymal transition and confers resistance to carboplatin in ovarian cancer cells. This study demonstrates, for the first time, that FSS-induced platinum resistance correlates with increased cellular protoporphyrin IX (PpIX), the penultimate downstream product of heme biosynthesis, the production of which can be enhanced using the clinically approved pro-drug aminolevulinic acid (ALA). These data suggest that, with further investigation, PpIX could serve as a fluorescence-based biomarker of FSS-induced platinum resistance. Additionally, this study investigates the efficacy of PpIX-enabled photodynamic therapy (PDT) and the secretion of extracellular vesicles under static and FSS conditions in Caov-3 and NIH:OVCAR-3 cells, two representative cell lines for high-grade serous ovarian carcinoma (HGSOC), the most lethal form of the disease. FSS induces resistance to ALA-PpIX-mediated PDT, along with a significant increase in the number of EVs. Finally, the ability of PpIX-mediated photodynamic priming (PDP) to enhance carboplatin efficacy under FSS conditions is quantified. These preliminary findings in monolayer cultures necessitate additional studies to determine the feasibility of PpIX as a fluorescence-based indicator, and mediator of PDP, to target chemoresistance in the context of FSS.

Overcoming the effects of fluid shear stress in ovarian cancer cell lines: Doxorubicin alone or photodynamic priming to target platinum resistance.

Resistance to platinum-based chemotherapies remains a significant challenge in advanced-stage high-grade serous ovarian carcinoma, and patients with malignant ascites face the poorest outcomes. It is, therefore, important to understand the effects of ascites, including the associated fluid shear stress (FSS), on phenotypic changes and therapy response, specifically FSS-induced chemotherapy resistance and the underlying mechanisms in ovarian cancer. This study investigated the effects of FSS on response to cisplatin, a platinum-based chemotherapy, and doxorubicin, an anthracycline, both of which are commonly used to manage advanced-stage ovarian cancer. Consistent with prior research, OVCAR-3 and Caov-3 cells cultivated under FSS demonstrated significant resistance to cisplatin. Examination of the role of mitochondria revealed an increase in mitochondrial DNA copy number and intracellular ATP content in cultures grown under FSS, suggesting that changes in mitochondria number and metabolic activity may contribute to platinum resistance. Interestingly, no resistance to doxorubicin was observed under FSS, the first such observation of a lack of resistance under these conditions. Finally, this study demonstrated the potential of photodynamic priming using benzoporphyrin derivative, a clinically approved photosensitizer that localizes in part to mitochondria and endoplasmic reticula, to enhance the efficacy of cisplatin, but not doxorubicin, thereby overcoming FSS-induced platinum resistance.

Treatment Outcome in Patients with Disseminated Cysticercosis: A Systematic Review of Case Reports and Case Series.

Disseminated cysticercosis is defined by multiple brain lesions and involvement of other body sites. Cysticidal treatment in disseminated cysticercosis is considered life-threatening. We conducted a systematic review of all published cases and case series to assess the safety and efficacy of cysticidal treatment. We conducted a systematic review in accordance with Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines (PROSPERO CRD42022331895) to assess the safety and efficacy of cysticidal treatment. Using the search term "disseminated neurocysticercosis OR disseminated cysticercosis," databases like PubMed, Scopus, Embase, and Google Scholar were searched. Outcomes included death and secondary measures like clinical improvement and lesion reduction. We calculated the predictors of primary outcome (death) using the binary logistic regression analysis. We reviewed 222 published cases from 101 publications. Approximately 87% cases were reported from India. Of 222 cases, 134 (60%) received cysticidal treatment. Follow-up information was available from 180 patients, 11 of them died, and 169 showed clinical improvement. The death rate was 4% (5 out of 114) in patients treated with cysticidal drugs plus corticosteroids, in comparison with 13% (5 out of 38) in patients who were treated with corticosteroids alone. All patients using only praziquantel faced fatality. Death predictors identified were altered sensorium and lack of treatment with albendazole. We noted that the risk of death after cysticidal treatment is not as we expected, and a multicentric randomized controlled trial is needed to resolve this issue.

Clinical features, pathogenesis, pathology, neuroimaging, clinical course and outcome of measles inclusion-body encephalitis: a systematic review of published case reports and case series.

Measles inclusion-body encephalitis (MIBE) is rare, with insights largely from case studies. We systematically analyzed subacute Sclerosing Panencephalitis (SSPE) cases in immunocompromised patients, identifying distinctive clinical and neuroimaging features. These findings could facilitate MIBE diagnosis without the need for brain biopsies. Our systematic review on MIBE and HIV-related SSPE adhered to PRISMA guidelines and was registered with PROSPERO. We searched multiple databases and followed a detailed inclusion process with independent reviews and quality assessment. Data on patient demographics, clinical features, and outcomes were compiled. A review of 39 studies on 49 MIBE patients and 8 reports on HIV-positive SSPE patients was conducted. Acute lymphoblastic leukemia, HIV, organ transplants, and malignancies were common precursors to MIBE. Perinatal HIV was prevalent among SSPE cases. Seizures were the primary symptom in MIBE, often drug-resistant and progressing to status epilepticus or epilepsia partialis continua, whereas periodic myoclonus was universal in SSPE. Neuroimaging showed distinct patterns for each group, and histopathology confirmed measles virus presence in 39% of MIBE cases. MIBE patients typically progressed to coma and death. In conclusion, MIBE and SSPE in HIV-infected patients present with distinct clinical pictures but identical brain pathological abnormalities.

The spectrum of psychiatric manifestations in subacute sclerosing panencephalitis: A systematic review of published case reports and case series.

Data related to psychiatric manifestations in subacute sclerosing panencephalitis (SSPE) is currently available only in the form of isolated case reports. In this systematic review, we evaluated the spectrum of psychiatric manifestations and their impact on the course and outcome of SSPE. Data were obtained from 4 databases (PubMed, Embase, Scopus, and Google Scholar), with the most recent search conducted on March 27, 2023. The PRISMA guidelines were followed, and the PROSPERO registration number for the protocol is CRD42023408227. SSPE was diagnosed using Dyken's criteria. Extracted data were recorded in an Excel spreadsheet. To evaluate the quality of the data, the Joanna Briggs Institute Critical Appraisal tool was employed. Our search resulted in 30 published reports of 32 patients. The mean age was 17.9 years. Schizophrenia, catatonia, and poorly characterized psychotic illnesses were the 3 most common psychiatric presentations that were seen in 63% (20/32) of cases. Catatonia was seen in 4 patients. Affective disorders, mania, and depression were reported among 22% (7/32) cases. In approximately 81% (26/32) cases, the course of SSPE was acute fulminant. Treatment with antipsychotic drugs had poor or no response. Out of 17 patients, who received antipsychotic drugs, 6 patients noted severe extrapyramidal adverse effects. SSPE often masquerades as a psychiatric disorder. Unresponsive psychiatric symptoms, early extrapyramidal signs, and progressive encephalopathy indicate SSPE.

Exposure to select PFAS and PFAS mixtures alters response to platinum-based chemotherapy in endometrial cancer cell lines.

BACKGROUND: Exposure to per- and poly-fluoroalkyl substances (PFAS) has been associated with significant alterations in female reproductive health. These include changes in menstrual cyclicity, timing of menarche and menopause, and fertility outcomes, as well as increased risk of endometriosis, all of which may contribute to an increased risk of endometrial cancer. The effect of PFAS on endometrial cancer cells, specifically altered treatment response and biology, however, remains poorly studied. Like other gynecologic malignancies, a key contributor to lethality in endometrial cancer is resistance to chemotherapeutics, specifically to platinum-based agents that are used as the standard of care for patients with advanced-stage and/or recurrent disease. OBJECTIVES: To explore the effect of environmental exposures, specifically PFAS, on platinum-based chemotherapy response and mitochondrial function in endometrial cancer. METHODS: HEC-1 and Ishikawa endometrial cancer cells were exposed to sub-cytotoxic nanomolar and micromolar concentrations of PFAS/PFAS mixtures and were treated with platinum-based chemotherapy. Survival fraction was measured 48-h post-chemotherapy treatment. Mitochondrial membrane potential was evaluated in both cell lines following exposure to PFAS ± chemotherapy treatment. RESULTS: HEC-1 and Ishikawa cells displayed differing outcomes after PFAS exposure and chemotherapy treatment. Cells exposed to PFAS appeared to be less sensitive to carboplatin, with instances of increased survival fraction, indicative of platinum resistance, observed in HEC-1 cells. In Ishikawa cells treated with cisplatin, PFAS mixture exposure significantly decreased survival fraction. In both cell lines, increases in mitochondrial membrane potential were observed post-PFAS exposure ± chemotherapy treatment. DISCUSSION: Exposure of endometrial cancer cell lines to PFAS/PFAS mixtures had varying effects on response to platinum-based chemotherapies. Increased survival fraction post-PFAS + carboplatin treatment suggests platinum resistance, while decreased survival fraction post-PFAS mixture + cisplatin exposure suggests enhanced therapeutic efficacy. Regardless of chemotherapy sensitivity status, mitochondrial membrane potential findings suggest that PFAS exposure may affect endometrial cancer cell mitochondrial functioning and should be explored further.

Transient fluid flow improves photoimmunoconjugate delivery and photoimmunotherapy efficacy.

Circulating drugs in the peritoneal cavity is an effective strategy for advanced ovarian cancer treatment. Photoimmunotherapy, an emerging modality with potential for the treatment of ovarian cancer, involves near-infrared light activation of antibody-photosensitizer conjugates (photoimmunoconjugates) to generate cytotoxic reactive oxygen species. Here, a microfluidic cell culture model is used to study how fluid flow-induced shear stress affects photoimmunoconjugate delivery to ovarian cancer cells. Photoimmunoconjugates are composed of the antibody, cetuximab, conjugated to the photosensitizer, and benzoporphyrin derivative. Longitudinal tracking of photoimmunoconjugate treatment under flow conditions reveals enhancements in subcellular photosensitizer accumulation. Compared to static conditions, fluid flow-induced shear stress at 0.5 and 1 dyn/cm2 doubled the cellular delivery of photoimmunoconjugates. Fluid flow-mediated treatment with three different photosensitizer formulations (benzoporphyrin derivative, photoimmunoconjugates, and photoimmunoconjugate-coated liposomes) led to enhanced phototoxicity compared to static conditions. This study confirms the fundamental role of fluid flow-induced shear stress in the anti-cancer effects of photoimmunotherapy.

Multicenter comparison of head shape outcomes for three minimally invasive strip craniectomy techniques for sagittal craniosynostosis.

OBJECTIVE: A literature gap exists comparing whole head shape outcome following correction of sagittal craniosynostosis. The objective of this multicenter study was to provide an analysis of long-term results following three different endoscopic strip craniectomy techniques for correction of sagittal craniosynostosis: 1) spring-assisted strip craniectomy, 2) wide-strip craniectomy with biparietal and bitemporal barrel-stave wedge osteotomies plus helmet orthosis, and 3) narrow-strip craniectomy plus orthosis without barrel staves. METHODS: Pre- and postoperative 3D stereophotogrammetric images were collected from patients who underwent craniosynostosis surgery. Procedures were divided among institutions as follows: spring-assisted strip craniectomies were performed at Atrium Health Wake Forest Baptist Hospital; narrow-strip craniectomies were performed at St. Louis Children's Hospital by one craniofacial surgeon; and wide-vertex craniectomies were performed at St. Louis Children's Hospital prior to 2010, and then continued at Children's Medical Center Dallas. Pre- and postoperative 3D whole-head composite images were generated for each procedure to visually represent outcomes at final follow-up and compared with age-matched normal controls. RESULTS: Patients in the spring-assisted strip craniectomy group showed normalization of frontal bossing and skull height compared with age-matched controls, whereas patients undergoing wide-strip craniectomy showed greater correction of occipital protrusion. Patients in the narrow-strip craniectomy cohort had intermediate results between these outcomes. Nested aggregate head shapes showed good correction of head shapes from all techniques. CONCLUSIONS: This large, retrospective, multicenter study illustrated whole head shape outcomes from three different craniectomy procedures. Although each procedure showed some differences in loci of primary correction, all three surgical methods demonstrated good correction of primary scaphocephalic deformity.

Tumor Necrosis Factor-α, CD1A and CD1E Genetic Polymorphisms in Guillain-Barré Syndrome: A Study from India.

Background: Guillain-Barré Syndrome (GBS) is an acute acquired autoimmune inflammatory disorder of peripheral nerves and roots. The pathogenesis is essentially an aberrant post-infectious immune response in a genetically susceptible host milieu. Single nucleotide polymorphisms (SNP) in genes encoding the inflammatory mediators like TNF-α, CD1A and CD1E can influence their expression and level and the susceptibility and clinical course of disease in GBS. Objective: We tried to study the susceptibility of single nucleotide polymorphisms of TNF-α and CD1 genes in Guillain-Barré Syndrome in Indian population and determine the association in terms of genotype, allele and haplotype distribution along with individual subtype, severity and clinical outcome. Methodology: In this case-control study, we investigated the single nucleotide polymorphism pattern in the promoter region of TNF-α (-308 G/A), TNF-α (-863C/A), CD1A and CD1E genes using real-time polymerase chain reaction in 75 GBS patients and analysed in comparison with 75 age and sex-matched healthy controls. Results: The findings revealed that the allelic distribution of TNF-α (-308 G/A) *A allele was associated with GBS (P value 0.04, Odds Ratio 2.03, 95% Confidence Interval 1.01-4.07). There was no association found with genotype, haplotype combination and other allele distribution for GBS in the study. CD1A and CD1E SNPs did not reveal any susceptibility for GBS. The subtype analysis did not reveal any statistical significance, except for CD1A *G allele with AMAN subtype (P value 0.026). The haplotypic combinations and mutant allele of TNF-α (-308 G/A), TNF-α (-863C/A), CD1A and CD1E were significantly associated with severe GBS in the study. However, there was no association of any SNP for mortality and survival of GBS in the study. Conclusion: TNF-α (-308 G/A)*A allele might confer genetic susceptibility for GBS in Indian population. CD1 genetic polymorphism could not be considered for susceptibility to GBS. TNF-α and CD1 genetic polymorphism did not affect mortality in GBS.

Methods to Evaluate Changes in Mitochondrial Structure and Function in Cancer.

Mitochondria are regulators of key cellular processes, including energy production and redox homeostasis. Mitochondrial dysfunction is associated with various human diseases, including cancer. Importantly, both structural and functional changes can alter mitochondrial function. Morphologic and quantifiable changes in mitochondria can affect their function and contribute to disease. Structural mitochondrial changes include alterations in cristae morphology, mitochondrial DNA integrity and quantity, and dynamics, such as fission and fusion. Functional parameters related to mitochondrial biology include the production of reactive oxygen species, bioenergetic capacity, calcium retention, and membrane potential. Although these parameters can occur independently of one another, changes in mitochondrial structure and function are often interrelated. Thus, evaluating changes in both mitochondrial structure and function is crucial to understanding the molecular events involved in disease onset and progression. This review focuses on the relationship between alterations in mitochondrial structure and function and cancer, with a particular emphasis on gynecologic malignancies. Selecting methods with tractable parameters may be critical to identifying and targeting mitochondria-related therapeutic options. Methods to measure changes in mitochondrial structure and function, with the associated benefits and limitations, are summarized.

Vision Loss in Subacute Sclerosing Panencephalitis: A Systematic Review of Case Reports and Case Series.

Vision loss is a presenting complaint in many patients with subacute sclerosing panencephalitis (SSPE). Data related to vision loss in SSPE is available only in the form of case reports. In this systematic review, we evaluated characteristics of vision loss, affected anatomic site, and patient course and outcome. We extracted data from four databases: PubMed, Embase, Scopus, and Google Scholar. The last search was done on October 26, 2022. We adhered to Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. The protocol was registered with PROSPERO (CRD42022362652). Dyken's criteria were used for the diagnosis of SSPE. The data were recorded in an Excel sheet. The Joanna Briggs Institute Critical Appraisal tool was used to assess the quality of data. The mean age of patients with SSPE was 17.9 years. Males outnumbered females (60:34). In 73 patients (76%), duration of illness/onset of vision loss was less than 6 months. In 76% patients (n = 73), visual manifestations appeared before encephalopathy. Involvement of the retina (58 of 96, 60.4%), optic nerve (9 of 96, 9.3%), or cerebral cortex (29 of 96, 30.2%) was responsible for vision loss. T2/fluid-attenuated inversion recovery (FLAIR) magnetic resonance imaging (MRI) parieto-occipital hyperintensities were the most frequent (71.4%) neuroimaging abnormality. Retinal biopsy revealed similar findings revealed by brain histopathology. All patients died and became akinetic mute during the follow-up period, which ranged from a few weeks to a few years. In conclusion, retinal involvement was the most common cause of vision loss. Vision loss often precedes encephalopathy. Cortical vision loss was associated invariably with T2/FLAIR MRI hyperintensities in the parieto-occipital region.

Case Report: An Unusual Case of Subacute Sclerosing Panencephalitis with Distinctive Clinical and Neuroimaging Features.

Subacute sclerosing panencephalitis (SSPE) is a relentlessly progressive brain disorder with invariable mortality. Subacute sclerosing panencephalitis is common in measles-endemic areas. We report an unusual SSPE patient with distinctive clinical and neuroimaging features. A 9-year-old boy came with a 5-month history of spontaneously dropping objects from both hands. Subsequently, he developed mental decline, a loss of interest in his surroundings, decreased verbal output, and inappropriate crying and laughing along with generalized periodic myoclonus. On examination, the child was akinetic mute. The child demonstrated intermittent generalized axial dystonic storm with flexion of upper limbs, an extension of lower limbs, and opisthotonos. Dystonic posturing was more dominant on the right side. Electroencephalography revealed periodic discharges. Cerebrospinal fluid antimeasles IgG antibody titer was markedly elevated. Magnetic resonance imaging revealed marked diffuse cerebral atrophy, and periventricular T2/fluid-attenuated inversion recovery hyperintensity. T2/fluid-attenuated inversion recovery images also revealed multiple cystic lesions present in the region of periventricular white matter. The patient was given a monthly injection of intrathecal interferon-α. The patient is currently continuing in the akinetic-mute stage. In conclusion, in this report, we described an unusual case of acute fulminant SSPE in which neuroimaging demonstrated unusual multiple small discrete cystic lesions in the cortical white matter. The pathological nature of these cystic lesions currently is not clear and needs to be explored.

Severe COVID-19-associated hyperinflammatory syndrome versus classic hemophagocytic lymphohistiocytosis: similarities, differences, and the way forward.

The hyperinflammatory immune response in severe COVID-19 infection shares features with secondary hemophagocytic lymphohistiocytosis (sHLH) in the form of fever, cytopenia, elevated inflammatory markers, and high mortality. There are contrasting opinions regarding utility of HLH 2004 or HScore in the diagnosis of severe COVID-19-related hyperinflammatory syndrome (COVID-HIS). This was a retrospective study of 47 patients of severe COVID-19 infection, suspected to have COVID-HIS and 22 patients of sHLH to other illnesses, to evaluate the diagnostic utility and limitations of HLH 2004 and/or HScore in context to COVID-HIS and to also evaluate the utility of Temple criteria for predicting severity and outcome in COVID-HIS. Clinical findings, hematological, and biochemical parameters along with the predictor of mortality were compared between two groups. Only 6.4% (3/47) of cases fulfilled ≥5/8 HLH 2004 criteria and only 40.52% (19/47) of patients showed HScore >169 in COVID-HIS group. 65.9% (31/47) satisfied the Temple criteria in COVID-HIS as compared with 40.9% (9/22) in the non-COVID group (p = 0.04). Serum ferritin (p = 0.02), lactate dehydrogenase (p = 0.02), direct bilirubin (p = 0.02), and C-reactive protein (p = 0.03) were associated with mortality in COVID-HIS. Both HScore and HLH-2004 criteria perform poorly for identifying COVID-HIS. Presence of bone marrow hemophagocytosis may help to identify about one-third of COVID-HIS missed by the Temple Criteria.

Photochemical Targeting of Mitochondria to Overcome Chemoresistance in Ovarian Cancer †.

Ovarian cancer is the most lethal gynecologic malignancy with a stubborn mortality rate of ~65%. The persistent failure of multiline chemotherapy, and significant tumor heterogeneity, has made it challenging to improve outcomes. A target of increasing interest is the mitochondrion because of its essential role in critical cellular functions, and the significance of metabolic adaptation in chemoresistance. This review describes mitochondrial processes, including metabolic reprogramming, mitochondrial transfer and mitochondrial dynamics in ovarian cancer progression and chemoresistance. The effect of malignant ascites, or excess peritoneal fluid, on mitochondrial function is discussed. The role of photodynamic therapy (PDT) in overcoming mitochondria-mediated resistance is presented. PDT, a photochemistry-based modality, involves the light-based activation of a photosensitizer leading to the production of short-lived reactive molecular species and spatiotemporally confined photodamage to nearby organelles and biological targets. The consequential effects range from subcytotoxic priming of target cells for increased sensitivity to subsequent treatments, such as chemotherapy, to direct cell killing. This review discusses how PDT-based approaches can address key limitations of current treatments. Specifically, an overview of the mechanisms by which PDT alters mitochondrial function, and a summary of preclinical advancements and clinical PDT experience in ovarian cancer are provided.

Open Versus Minimally Invasive Approach for Craniosynostosis: Analysis of the National Surgical Quality Improvement Program-Pediatric.

OBJECTIVE: This multicenter study aimed to compare demographic, operative, and short-term outcomes data between open and minimally invasive surgical approaches for craniosynostosis repair utilizing the American College of Surgeon's National Surgical Quality Improvement Program Pediatric (NSQIP-P) database and highlight surgical disparities among races and ethnicities. DESIGN: Retrospective review of large multicenter database. SETTING: Freestanding general acute care children's hospitals, children's hospitals within a larger hospital, specialty children's hospitals, or general acute care hospitals with a pediatric wing. PATIENTS AND PARTICIPANTS: A total of 4931 pediatric patients underwent craniosynostosis correction within the NSQIP-P database from 2013 to 2019. INTERVENTIONS: None. MAIN OUTCOME MEASURE(S): Demographic information included age at surgery, sex, race, and ethnicity. Operative and outcomes measures included operative time, anesthesia time, days until discharge, postoperative complications, blood transfusions, 30-day readmission, and 30-day unplanned return to operating room. RESULTS: Patients who underwent minimally invasive surgery had significantly shorter operative and anesthesia times (p < .001; p < .001), fewer days until discharge (p < .001), fewer postoperative complications (p < .05), and less blood transfusions (p < .001). The proportion of White patients was significantly higher in the minimally invasive surgery group (p < .01), whereas Black and Hispanic patients had a significantly higher proportion in the open surgery group (p < .001; p < .001). Additionally, the percentage of patients undergoing minimally invasive surgery increased from 3.8% in 2014 to over 13% in 2019. CONCLUSIONS: This study adds to a growing consensus that minimally invasive surgery has significantly decreased operative time, anesthesia time, transfusion rates, length of hospital stay, and postoperative complications compared to open surgery. Racial and ethnic surgical disparities showed larger proportions of Black and Hispanic populations undergoing open procedures.

Photodynamic Priming Overcomes Per- and Polyfluoroalkyl Substance (PFAS)-Induced Platinum Resistance in Ovarian Cancer†.

Per- and polyfluoroalkyl substances (PFAS) are widespread environmental contaminants linked to adverse outcomes, including for female reproductive biology and related cancers. We recently reported, for the first time, that PFAS induce platinum resistance in ovarian cancer, potentially through altered mitochondrial function. Platinum resistance is a major barrier in the management of ovarian cancer, necessitating complementary therapeutic approaches. Photodynamic therapy (PDT) is a light-based treatment modality that reverses platinum resistance and synergizes with platinum-based chemotherapy. The present study is the first to demonstrate the ability of photodynamic priming (PDP), a low-dose, sub-cytotoxic variant of PDT, to overcome PFAS-induced platinum resistance. Comparative studies of PDP efficacy using either benzoporphyrin derivative (BPD) or 5-aminolevulinic acid-induced protoporphyrin IX (PpIX) were conducted in two human ovarian cancer cell lines (NIH:OVCAR-3 and Caov-3). BPD and PpIX are clinically approved photosensitizers that preferentially localize to, or are partly synthesized in, mitochondria. PDP overcomes carboplatin resistance in PFAS-exposed ovarian cancer cells, demonstrating the feasibility of this approach to target the deleterious effects of environmental contaminants. Decreased survival fraction in PDP + carboplatin treated cells was accompanied by decreased mitochondrial membrane potential, suggesting that PDP modulates the mitochondrial membrane, reducing membrane potential and re-sensitizing ovarian cancer cells to carboplatin.

Photodynamic Stromal Depletion Enhances Therapeutic Nanoparticle Delivery in 3D Pancreatic Ductal Adenocarcinoma Tumor Models.

Pancreatic ductal adenocarcinoma (PDAC) is among the most lethal of human malignancies. PDAC is characterized by dense fibrous stroma which obstructs drug delivery and plays complex tumor-promoting roles. Photodynamic therapy (PDT) is a light-based modality which has been demonstrated to be clinically feasible and effective for tumors of the pancreas. Here, we use in vitro heterocellular 3D co-culture models in conjunction with imaging, bulk rheology and microrheology to investigate photodegradation of non-cellular components of PDAC stroma (photodynamic stromal depletion, PSD). By measuring the rheology of extracellular matrix (ECM) before and after PDT we find that softening of ECM is concomitant with increased transport of nanoparticles (NPs). At the same time, as shown by us previously, photodestruction of stromal fibroblasts leads to enhanced tumor response to PDT. Here we specifically evaluate the capability of PSD to enhance RNA nanomedicine delivery, using a NP carrying an inhibitor of miR-21-5P, a PDAC oncomiR. We confirm improved delivery of this therapeutic NP after PSD by observation of increased expression of PDCD4, a protein target of miR-21-5P. Collectively, these results in 3D tumor models suggest that PSD could be developed to enhance delivery of other cancer therapeutics and improve tumor response to treatment.

Value of whole-body MRI for the assessment of response to albendazole in disseminated neurocysticercosis: a prospective follow-up study.

BACKGROUND: Disseminated neurocysticercosis is defined as simultaneous involvement of the brain (≥3 cysts) and at least one additional body site/organ. We aimed to identify disseminated cystic lesions in other body parts and investigate the effect of albendazole. METHODS: We enrolled patients with multiple (≥3) neurocysticercosis brain lesions. Whole-body MRI (short tau inversion recovery coronal sequences) was performed to assess the number of lesions in the brain and other body parts at baseline and 3 months after albendazole therapy. RESULTS: We screened 35 patients with multiple brain neurocysticercosis. In 13 patients, whole-body MRI demonstrated disseminated neurocysticercosis lesions. Ten patients were treated with albendazole. We excluded three patients. Brain MRI showed a mean lesion count of 163.6±193.8. Whole-body MRI (excluding the brain) showed a mean lesion count of 629.9±486.1. After albendazole therapy, the lesion load of the brain reduced significantly (163.6±193.8 to 99±178.3; p=0.008). Similarly, whole-body MRI showed a significant reduction in extracerebral neurocysticercosis lesion load (629.9±486.1 to 183.4±301.9; p=0.005). Three patients had complete resolution, five patients showed ≥50% reduction and two patients had <50% reduction in extracerebral lesion load. CONCLUSION: Whole-body MRI should routinely be performed in multiple neurocysticercosis lesions of the brain. Albendazole treatment leads to a remarkable reduction in neurocysticercosis lesions throughout the body.