Monolithic silicon microlens arrays for far-infrared astrophysics.

Future far-infrared astrophysics observatories will require focal plane arrays containing thousands of ultrasensitive, superconducting detectors, each of which require efficient optical coupling to the telescope fore-optics. At longer wavelengths, many approaches have been developed, including feedhorn arrays and macroscopic arrays of lenslets. However, with wavelengths as short as 25 µm, optical coupling in the far infrared remains challenging. In this paper, we present an approach to fabricate far-infrared monolithic silicon microlens arrays using grayscale lithography and deep reactive ion etching. The fabricated microlens arrays presented here are designed for two different wavebands: 25-40 µm and 135-240 µm. The microlens arrays have sags as deep as 150 µm, are hexagonally packed with a pixel pitch of 900 µm, and have an overall size as large as 80 by 15 mm. We compare an as-fabricated lens profile to the design profile and calculate that the fabricated lenses would achieve 84% encircled power for the designed detector, which is only 3% less than the designed performance. We also present methods developed for antireflection coating microlens arrays and for a silicon-to-silicon die bonding process to hybridize microlens arrays with detector arrays.

Lymphoscintigraphy Using Tilmanocept Detects Multiple Sentinel Lymph Nodes in Melanoma Patients.

BACKGROUND: Technetium-99m-labeled Tilmanocept, a multivalent mannose, is readily internalized by the CD206 surface receptor on macrophages and dendritic cells which are abundantly present in lymph nodes. We want to examine the drainage patterns of Technetium-99m-labeled Tilmanocept to sentinel lymph nodes (SLNs) in melanoma patients following the 10% rule. METHODS: Multi-center retrospective review of patients with cutaneous melanoma undergoing SLN biopsy using Technetium-99m-labeled Tilmanocept between 2008 and 2014 was conducted. Statistical methods were used for data analyses. RESULTS: Of the 564 patients (mean age of 60.3 and 62% male) with preoperative lymphoscintigraphy showing at least one SLN, several primary tumor sites were included: 27% head/neck, 33% trunk, 21% upper extremity and 19% lower extremity. For the head/neck primary site, 36.5% of patients had multiple draining basins; for the trunk site, 36.4% of patients; for the upper extremity site, 13% of patients; and for the lower extremity, 27.4% of patients. A median of 3 (range 1-18) SLNs were identified and resected. Overall, 78% of patients had >1 SLN identified by Technetium-99m-labeled Tilmanocept. In a multivariate model, patients with >1 SLN were significantly associated with age, Breslow depth, tumor location and higher AJCC tumor stage. A total of 17.7% of patients (100/564) had a positive SLN identified. A total of 145 positive SLNs were identified out of 1,812 SLNs with a positive SLN rate of 8%. Positive SLN status was significantly associated with younger age, greater Breslow depth, mitosis rate, higher AJCC tumor stage, presence of ulceration and angiolymphatic invasion. CONCLUSIONS: Using the 10% rule, Technetium-99m-labeled Tilmanocept detects multiple SLNs in most melanoma patients.

Factors associated with revision surgery for olecranon bursitis after bursectomy.

BACKGROUND: The primary aim of our study was to identify the factors associated with revision surgery after bursal excision in patients with olecranon bursitis. The secondary aims were to describe the revision rate after bursectomy and to assess which factors are associated with flap surgery after bursectomy and describe the most common complications after bursectomy of the olecranon bursa. METHODS: We included 191 adult patients with olecranon bursitis who underwent olecranon bursa excision between January 2002 and October 2018. Patients who were pregnant, patients with incomplete records of the primary surgical procedure, and patients who underwent bursectomy during elbow arthroplasty were excluded. After manual chart review, we found that 22 patients had undergone revision surgery. Bivariate analysis was performed to assess the association between revision surgery and patient characteristics, comorbidities, and clinical characteristics. Additionally, we collected data regarding postoperative complications and intraoperative variables such as the use of drains, vacuum assisted closure therapy, and flap surgery. RESULTS: The overall revision rate in our cohort was 11.5% (22 of 191 patients). Bivariate analysis showed that patients who underwent revision surgery were more frequently women (P = .004), more often had a history of ipsilateral (P = .020) or contralateral (P = .012) olecranon bursitis, and more often received a diagnosis of rheumatoid arthritis (P = .001) or diabetes mellitus (P = .019). The most common complications were delayed wound healing (n = 8, 4.2%) and osteomyelitis (n = 8, 4.2%). Flap surgery was performed in 5 patients (2.6%). Bivariate analysis showed that patients with rheumatoid arthritis underwent flap surgery more frequently (P = .011). CONCLUSION: The revision rate after bursectomy for olecranon bursitis was 11.5% (22 of 191 patients). Patients with rheumatoid arthritis, diabetes mellitus, or a history of ipsilateral and contralateral olecranon bursitis and female patients underwent revision surgery after bursectomy for olecranon bursitis more frequently. In addition, patients with rheumatoid arthritis underwent flap surgery after bursectomy more frequently.

Evaluating the Effects of COVID-19 on Plastic Surgery Emergencies: Protocols and Analysis From a Level I Trauma Center.

BACKGROUND: The COVID-19 crisis has brought many unique challenges to the health care system. Across the United States, social distancing measures have been put in place, including stay-at-home (SAH) orders, to combat the spread of this infection. This has impacted the type and volume of traumatic injuries sustained during this time. Meanwhile, steps have been taken in our health care system to assure that adequate resources are available to maintain a high standard of patient care while recognizing the importance of protecting health care providers. Using comparative data, we aim to describe the trends in traumatic injuries managed by our plastic surgery service and detail the changes in consultation policies made to minimize provider exposure. METHODS: A retrospective chart review was performed of all plastic surgery emergencies at our institution during the 3 weeks preceding the issuance of SAH orders in Chicago and the 3 weeks after. The electronic medical record was queried for patient age, type and mechanism of injury, location where injury was sustained, presence of domestic violence, length of inpatient hospital stays, and treatment rendered. The two 3-week periods were then comparatively analyzed to determine differences and trends in these variables and treatment rendered. The 2 periods were then comparatively analyzed to determine differences and trends in these variables. RESULTS: There was a significant decrease in trauma consults since the issuance of SAH (88 pre-SAH vs 62 post-SAH) with a marked decrease in trauma-related hand injuries. There was an increase in the percentage of assault-related injuries including those associated with domestic violence, whereas there was an overall decrease in motor vehicle collisions. There was no notable change in the location where injuries were sustained. Significantly fewer patients were seen by house staff in the emergency room, whereas those requiring surgical intervention were able to receive care without delay. CONCLUSIONS: Stay-at-home orders in Chicago have impacted traumatic injury patterns seen by the Section of Plastic and Reconstructive Surgery at a level I Trauma Center. Safe and timely care can continue to be provided with thorough communication, vigilance, and guidance from our colleagues.

Development and Characterization of Neutralizing Antibodies Against Zaire Ebolavirus Glycoprotein and Protein 40.

BACKGROUND/AIMS: Monoclonal antibodies (mAbs) are presently the most promising treatment against Ebola virus disease (EVD), and cocktail of two or more antibodies likely confers protection through complementary mechanisms. Zaire Ebolavirus (EBOV) glycoprotein (GP) and viral protein 40 (VP40) are targets for designing neutralizing antibodies. Currently, the antiviral therapeutics of mAb-cocktails are still limited solely to anti-GP antibodies，there is no Abs cocktail against Zaire EBOV GP and VP40, which both have important interactions with host cellular membrane. METHODS: We used hybridoma technology to produce anti-Zaire EBOV GP mAb against GP receptor binding domain, and anti-Zaire EBOV VP40 mAbs against the N-terminal domain, the C-terminal domain, respectively; synthesized Zaire EBOV transcription and replication competent virus like particles (trVLPs), which model even all aspects of the EBOV life cycles in order to evaluate the anti-viral effect of mAbs. Then, we characterized the anti- Zaire EBOV trVLPs effect of anti-GP and VP40 mAbs in vitro by real time-PCR, immunofluorescence assay and western blot analysis. RESULTS: Our results demonstrate that anti-GP or anti-VP40 mAbs effectively inhibit trVLPs replication. The cocktails of anti-GP and anti-VP40 mAbs, or between anti-VP40 mAbs, had synergistic anti-trVLPs effect. Meanwhile, the detailed DNA and amino acid sequences of the mAbs were checked. CONCLUSION: The study verifies neutralizing efficacy of anti-GP or anti-VP40 mAb, report promising cocktail of anti-GP and anti-VP40 mAb, or cocktail of two anti-VP40 mAbs. To our knowledge, this is the first account to report the important anti-viral effect of cocktails of anti-GP and anti-VP40 mAbs in vitro.

Complications After Total Skin-Sparing Mastectomy and Expander-Implant Reconstruction: Effects of Radiation Therapy on the Stages of Reconstruction.

BACKGROUND: Many patients undergoing total-skin sparing mastectomy (TSSM) and 2-staged expander-implant (TE-I) reconstruction require postmastectomy radiation therapy (PMRT). Additionally, many patients undergoing TSSM for recurrent cancer have a history of lumpectomy and radiation therapy (XRT). Few studies have looked at the impact of XRT on the stages of TE-I reconstruction. METHODS: Patients undergoing TSSM and immediate TE-I reconstruction between 2006 and 2013 were identified from a prospectively maintained database. Rates of TE-I loss and severe infection requiring intravenous antibiotics were compared in patients with prior XRT (85 cases) and PMRT (133 cases). Complications were divided by stage of reconstruction: first stage (TSSM and TE placement) and second stage (TE-I exchange). RESULTS: Mean follow-up time was 2.5 years. Patients with prior XRT had more complications after the first stage of reconstruction than the second (TE-I loss: 15% vs 5%, P = 0.03; infection: 20% vs 8%, P = 0.04). Patients receiving PMRT had low complication rates after the first stage, when they had not yet received radiation (TE-I loss: 2%; infection: 5%). However, complication rates after TE-I exchange (TE-I loss, 18%; infection, 31%) were significantly higher, and nearly 4-fold higher than patients with prior XRT. CONCLUSIONS: Patients with prior XRT are at high risk for complications after the first stage of TE-I reconstruction after TSSM; however, the risk of complications at the second stage is comparable to patients without radiation exposure and significantly lower than patients receiving PMRT. Patients receiving radiation therapy should be given appropriate preoperative counseling regarding their risks.

MicroRNA Expression Profiling of Pancreatic Cancer Cell Line L3.6p1 Following B7-H4 Knockdown.

BACKGROUND/AIMS: Co-stimulating molecule B7-H4 regulates T cell-mediated immune responses, participates in tumor immune escape, and promotes the proliferation and metastasis of pancreatic cancer cells. However, the specific mechanisms are unclear. MicroRNAs (miRNAs) participated in the pathogenesis and progression of cancer. METHODS: In this study, a microarray technique was used to screen B7-H4-related differentially expressed miRNAs in a pancreatic cancer cell line find those associated with pancreatic cancer. Using a miRCURYTM LNA Array approach, we compared the miRNA expression profiles of L3.6p1 pancreatic cancer cells transfected with B7-H4 siRNA for 72 h with those transfected with non-target siRNAs. RESULTS: B7-H4 siRNA significantly up-regulated 57 miRNAs and down-regulated 14 miRNAs. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) Pathway analysis of predicted miRNA targets showed that these genes were mainly involved in protein binding, pathways in cancer, mitogen-activated protein kinase (MAPK) signaling pathway, and phosphatidylinositol 3-kinase-Akt (PI3K-Akt) signaling pathway. CONCLUSIONS: This is the first description of target genes of B7-H4, showing that miRNAs participate in the B7-H4 mediated regulation of oncogenicity and pathogenesis of pancreatic cancer. These results may help us better understand the role of B7-H4 in the progression of pancreatic cancer and its possible mechanisms. We also provide novel biomarkers for potential treatments of pancreatic cancer.

Recalcitrant Invasive Skin Cancer of the Scalp: Combined Extirpation and Microsurgical Reconstruction Without Cranioplasty.

BACKGROUND: Recurrent invasive skin cancer of the scalp and calvarium is a difficult problem for which universally accepted treatment protocols have not been established. The authors present their 10-year experience with treatment of this specific subset of scalp reconstruction patients and present a successful treatment algorithm that is well suited to this patient population. METHODS: The authors retrospectively reviewed all patients of microsurgical scalp reconstruction performed from 2005 to 2015 that involved invasive cutaneous malignancies of the scalp and calvarium. RESULTS: Eleven patients met inclusion criteria. There were 9 squamous cell carcinoma, 1 basal cell carcinoma, and 1 melanoma. Seven received radiation prior to resection, 2 were irradiated postoperatively, and 2 were immunosuppressed. Seven had a history of prior scalp reconstruction. The median scalp defect size was 141 cm. All the patients underwent craniectomy and the median cranial defect size was 71 cm. Cranioplasty was not performed in any patient. There were no intraoperative complications or flap loss. Recipient site complications included hematoma in 1, 1 seroma, 2 cerebral spinal fluid leaks, 3 partial skin graft loss. There was 1 donor site seroma in a patient who had a latissimus dorsi flap. All the patients reported satisfaction with the overall result and none were limited in activities by the existing cranial defect. CONCLUSIONS: This is the largest series published to date that focuses exclusively on management of cutaneous malignancies with intracranial invasion. Wide resection with craniectomy, and reconstruction with microvascular free tissue transfer without cranioplasty provides safe and reliable treatment of recalcitrant invasive scalp skin cancers with low morbidity and without major complications. Pre and postoperative radiation is well tolerated with this approach. The patients in this series were of advanced age and of a lifestyle for which cranioplasty is unnecessary for return to regular activities.

Rhinoplasty Results Are Influenced by Non-nasal Features.

Rhinoplasty results are evaluated both objectively and subjectively following any procedure by plastic surgeons and nonplastic surgeons at meetings, in publications, and online. We aim to evaluate whether subjective aesthetics of non-nasal features, such as the eyes and lips, would influence the overall evaluation of rhinoplasty results. We matched pairs of photographs of patients who had undergone aesthetic rhinoplasty by sex, age, and skin tone. We transferred the eyes/eyebrows and lips from the photographs of the donor patient onto the photographs of the original patient to create composite photographs. Plastic surgeons were asked to rate the rhinoplasty results objectively, and non-plastic surgeons were asked to rate the overall attractiveness of 16 sets of photographs (8 originals and 8 composites). Postoperative photographs that were deemed to be more attractive were associated with higher ratings of rhinoplasty improvement. The objective nasal result may be influenced by non-nasal aesthetic factors as rhinoplasty surgeons gave higher ratings to more attractive faces. Greater emphasis on neutralizing non-nasal factors in pre- and postoperative photographs should be considered.

Expanding the Indications for Total Skin-Sparing Mastectomy: Is It Safe for Patients with Locally Advanced Disease?

BACKGROUND: Indications for total skin-sparing mastectomy (TSSM) continue to expand. Although initially used only for early-stage breast cancer, TSSM currently is offered in many centers to patients with locally advanced disease. However, despite this practice change, limited data on oncologic outcomes in this population have been reported. METHODS: A retrospective review of a prospectively collected database of all patients undergoing TSSM and immediate reconstruction from 2005 to 2013 was performed. The outcomes for patients with stage 2b and stage 3 cancer were included in the analysis. The primary outcomes included the development of locoregional or distant recurrences. RESULTS: Of 753 patients undergoing TSSM, 139 (18 %) presented with locally advanced disease. Of these 139 patients, 25 (18 %) had stage 2b disease, and 114 (82 %) had stage 3 disease. Most of the patients (97 %) received chemotherapy (77 % neoadjuvant, 20 % adjuvant), whereas 3 % received adjuvant hormonal therapy alone. Of the neoadjuvant patients, 13 (12 %) had a pathologic complete response (pCR) to treatment. During a mean follow-up period of 41 months (range 4-111 months), seven patients (5 %) had a local recurrence, 21 patients (15.1 %) had a distant recurrence, and three patients (2.2 %) had simultaneous local and distant recurrences. None of the local recurrences occurred in the preserved nipple-areolar complex skin. CONCLUSIONS: Patients with locally advanced breast cancer are most at risk for distant rather than local recurrence, even after TSSM. When used in conjunction with appropriate multimodal therapy, TSSM is not associated with an increased risk for local recurrence in this population, even in the setting of low pCR rates.

Tissue Expander Reconstruction After Total Skin-Sparing Mastectomy: Defining the Effects of Coverage Technique on Nipple/Areola Preservation.

BACKGROUND: Total skin-sparing mastectomy (TSSM) has become increasingly frequent in recent years, as inclusion criteria continue to expand. Options for tissue expander coverage in these patients include complete submuscular tissue expander coverage and acellular dermal matrix (ADM)-assisted coverage. This study compares both techniques with regard to relevant outcomes, during a recent 1-year period at our institution. METHODS: All women undergoing TSSM and immediate expander placement between January 2012 and January 2013 were prospectively tracked. Patient demographics, expander coverage type, adjuvant treatment, length and characteristics of expansion, and incidence of complications were analyzed. RESULTS: In 1 year, 127 patients underwent TSSM on 202 breasts. Overall, 113 expanders underwent submuscular coverage, and 89 underwent ADM-assisted coverage. Mean intraoperative fill volume was 52 mL in the submuscular cohort and 205 mL in the ADM cohort (P = 0.0001). Mean tissue expander size was 404 mL in the submuscular cohort and 454 mL in the ADM cohort (P = 0.0002). χ analysis demonstrated no differences between the cohorts in incidence of complications, including partial/complete nipple necrosis. CONCLUSIONS: The use of ADM for expander coverage after TSSM allowed for greater initial expander fill. With large and ptotic breasts, this allows for reduced incidence of skin folds in the preserved breast skin pocket, and greater control over final nipple position, as the amount of loose, mobile skin is reduced by the greater initial fill. The safety profile of ADM use after TSSM is equivalent to that of submuscular coverage, with no differences in partial or complete nipple necrosis.

Tumor Involvement of the Nipple in Total Skin-Sparing Mastectomy: Strategies for Management.

BACKGROUND: Despite a growing body of literature on oncologic and reconstructive outcomes after total skin-sparing mastectomy (TSSM), some questions related to this approach remain unanswered, including strategies for managing tumor involvement of the nipple while maintaining the aesthetic benefits of TSSM. METHODS: A prospectively maintained database of patients undergoing TSSM and immediate breast reconstruction from 2005 to 2013 was reviewed. Outcomes included tumor involvement of resected nipple tissue and subsequent management, recurrences after nipple involvement, and trends in management of involved nipple tissue. RESULTS: The study included 1176 breasts in 751 patients treated with TSSM. The follow-up period was 31.3 months. The nipple-areolar complex (NAC) of 32 breasts (2.7 %) had a positive margin or involvement of nipple tissue. Of these breasts, 56 % contained invasive cancer, and 44 % had in situ disease. Management included repeat excision (11 cases, 34 % of cases), radiation of the NAC (as part of the postmastectomy breast field) without further excision (5 cases, 16 %), complete NAC removal (8 cases, 25 %), and no further treatment (8 cases, 25 %). Management by complete NAC skin excision significantly decreased during the study period (p = 0.003). The overall local recurrence rate was 6.2 %. No patients had recurrence in the preserved NAC skin. CONCLUSIONS: Despite expanding indications for TSSM, it can be performed safely with low rates of nipple involvement. Over time, tumor involvement of the nipple has been treated with re-excision or other alternative approaches to NAC removal that preserve the aesthetic benefits of total skin-sparing approaches without an early adverse impact on local recurrence.

Negative Genetic Testing Does Not Deter Contralateral Prophylactic Mastectomy in Younger Patients with Greater Family Histories of Breast Cancer.

BACKGROUND: Increasing rates of contralateral prophylactic mastectomy (CPM) correlate with adoption of total skin-sparing mastectomy (TSSM). We aimed to characterize patients with unilateral breast cancer who underwent TSSM with CPM or without CPM (No CPM). METHODS: We reviewed all patients with unilateral breast cancer who underwent TSSM from 2006 to 2013. Trends in CPM and genetic testing were evaluated across time. Patient characteristics and complications were compared between CPM and No CPM groups. RESULTS: We identified 591 patients (293 No CPM and 298 CPM) with median follow-up of 25 (interquartile range [IQR] 13-52) months. All patients with deleterious mutations and 58% of those who tested negative for mutations underwent CPM. In patients who tested negative for mutations, CPM was correlated with younger patient age, greater family history, and younger age of relatives diagnosed with breast/ovarian cancer. CPM was associated with an increased risk of superficial nipple necrosis (relative risk [RR] 2.1, 95% confidence interval [CI] 1.12-4.0), wound breakdown (RR 1.62, 95% CI 1.04-2.5), and infections requiring oral antibiotics (RR 1.59, 95% CI 1.16-2.2). In patients with tissue expander/implant reconstruction, CPM was associated with an increased risk of implant exposure (RR 1.95, 95% CI 1.03-3.7) but did not affect the risk of implant loss (RR 0.91, 95% CI 0.56-1.48). CONCLUSIONS: Patients who choose CPM fit the profile of patients with higher risk of contralateral breast cancer (CBC), which may be due to polygenic risk factors that are currently under investigation. Physicians should address patients' fears of CBC, screening concerns, and the risk of complications when considering CPM.

Total skin-sparing mastectomy and immediate breast reconstruction: an evolution of technique and assessment of outcomes.

BACKGROUND: Total skin-sparing mastectomy (TSSM) with preservation of the breast and nipple-areolar complex (NAC) skin was developed to improve aesthetic outcomes for mastectomy. Over time, indications for TSSM broadened and our technique has evolved with a series of systematic improvements. METHODS: We reviewed all cases of TSSM with immediate breast reconstruction performed from 2005 to 2012. Patient comorbidities, treatment characteristics, postoperative complications, and outcomes were obtained prospectively and through medical chart review. Locoregional recurrences, distant recurrences, and patient survival were analyzed with Kaplan-Meier methods. RESULTS: During this 8-year period, 633 patients (981 cases) underwent TSSM with median follow-up time of 29 (interquartile range 14-54) months. Immediate breast reconstruction was performed with tissue expander placement (89 %), pedicle TRAM (5 %), free flap (5 %), permanent implant (0.3 %), or latissimus flap (0.2 %). The incidences of postoperative complications decreased significantly over time. In 2012, these were down to 3.5 % for superficial nipple necrosis, 1.0 % for complete nipple necrosis, 3.0 % for minor skin flap necrosis, 4.4 % for major skin flap necrosis, 13.3 % for infections requiring oral antibiotics, 9.9 % for infections requiring intravenous antibiotics, 3.4 % for infections requiring operative intervention, and 8.5 % for expander/implant. Overall 5-year cumulative incidences of recurrence were 3.0 % (locoregional) and 4.2 % (distant), and there were no recurrences in the NAC skin. CONCLUSIONS: Systematic changes in our technique of TSSM and immediate breast reconstruction have decreased postoperative complications over time. Oncologic outcomes of locoregional and distal recurrences remain similar to skin-sparing mastectomy techniques.

Increased sensitivity of glioma cells to 5-fluorocytosine following photo-chemical internalization enhanced nonviral transfection of the cytosine deaminase suicide gene.

Despite advances in surgery, chemotherapy and radiotherapy, the outcomes of patients with GBM have not significantly improved. Tumor recurrence in the resection margins occurs in more than 80% of cases indicating aggressive treatment modalities, such as gene therapy are warranted. We have examined photochemical internalization (PCI) as a method for the non-viral transfection of the cytosine deaminase (CD) suicide gene into glioma cells. The CD gene encodes an enzyme that can convert the nontoxic antifungal agent, 5-fluorocytosine, into the chemotherapeutic drug, 5-fluorouracil. Multicell tumor spheroids derived from established rat and human glioma cell lines were used as in vitro tumor models. Plasmids containing either the CD gene alone or together with the uracil phosphoribosyl transferase (UPRT) gene combined with the gene carrier protamine sulfate were employed in all experiments.PCI was performed with the photosensitizer AlPcS2a and 670 nm laser irradiance. Protamine sulfate/CD DNA polyplexes proved nontoxic but inefficient transfection agents due to endosomal entrapment. In contrast, PCI mediated CD gene transfection resulted in a significant inhibition of spheroid growth in the presence of, but not in the absence of, 5-FC. Repetitive PCI induced transfection was more efficient at low CD plasmid concentration than single treatment. The results clearly indicate that AlPcS2a-mediated PCI can be used to enhance transfection of a tumor suicide gene such as CD, in malignant glioma cells and cells transfected with both the CD and UPRT genes had a pronounced bystander effect.

Pharmaceutical innovation and advanced biotechnology in the biotech-pharmaceutical industry for antibody-drug conjugate development.

Antibody-drug conjugates (ADCs), from prototypes in the 1980s to first- and second-generation products in the 2000s, and now in their multiformats, have progressed tremendously to meet oncological challenges. Currently, 13 ADCs have been approved for medical practice, with over 200 candidates in clinical trials. Moreover, ADCs have evolved into different formats, including bispecific ADCs, probody-drug conjugates, pH-responsive ADCs, target-degrading ADCs, and immunostimulating ADCs. Technologies from biopharmaceutical industries have a crucial role in the clinical transition of these novel biotherapeutics. In this review, we highlight several features contributing to the prosperity of bioindustrial ADC development. Various proprietary technologies from biopharmaceutical companies are discussed. Such advances in biopharmaceutical industries are the backbone for the success of ADCs in development and clinical application.

Changes in the amygdala produced by viewing strabismic eyes.

PURPOSE: The aim of this study was to look for the response to strabismus images in the limbic network (amygdala, hippocampus, parahippocampus) of healthy volunteers and to compare it with their reaction to viewing normal eyes. DESIGN: Prospective, observational study. PARTICIPANTS: Thirty-one healthy volunteers underwent functional magnetic resonance imaging (fMRI). METHODS: Functional magnetic resonance imaging data and blood oxygen level-dependent signal changes were analyzed using the BrainVoyager QX software package (Brain Innovation, Maastricht, The Netherlands). MAIN OUTCOME MEASURES: Responses to viewing strabismus images were compared with those observed while viewing normal eye images. RESULTS: Strabismus images led to significant activation of the amygdala, hippocampus, parahippocampal, and fusiform gyri in 30 of 31 subjects compared with normal eye images, indicating a negative emotional response. CONCLUSIONS: These fMRI results confirm that strabismus influences organically not only the patient with nonparallel eyes but also observers. Treatment of strabismus therefore changes the interpersonal dynamic for patients with strabismus on a demonstrable organic basis. FINANCIAL DISCLOSURE(S): The author(s) have no proprietary or commercial interest in any materials discussed in this article.

Maximum atropine dose without clinical signs or symptoms.

PURPOSE: Atropine 1% has been used to slow the progression of myopia; however, it has not gained worldwide clinical acceptance because it results in clinically significant pupillary mydriasis and accommodative paralysis. Lower concentrations of atropine (0.5 to 0.01%) have been reported to be associated with fewer symptoms, while still controlling myopia. It is the purpose of this study to find the highest concentration of atropine that does not result in significant symptoms from pupillary dilation and accommodative paralysis. METHODS: A 3 × 3 phase I clinical trial paradigm was used in 12 subjects, to determine the maximum dosage of atropine which could be prescribed without creating symptoms or clinical signs of insufficient accommodation or excessive pupillary dilation. Accommodation was measured by pushouts and pupillary dilation by photography. Prior to this study, we established the following criteria for comfort: 5D or more of residual amplitude of accommodation, less than or equal to a 3 mm pupillary difference between the eyes, and a report of minimal symptoms of near vision blur or outside photophobia. RESULTS: Our results indicate that atropine 0.02% is the highest concentration that did not result in clinical symptoms and findings associated with higher dosages. Mean pupillary dilation was 3 mm, and mean accommodative amplitude was 8 diopters with this concentration. Further, reduction of the concentration of atropine from 0.02 to 0.01% did not seem to result in a decrease in clinical signs or symptoms associated with atropine. CONCLUSIONS: Atropine 0.02% is the highest concentration that does not produce significant clinical symptoms from accommodation paresis or pupillary dilation. This would be an appropriate starting point in evaluating a low dosage of atropine to slow myopic progression.

Reoperation Following Zone II Flexor Tendon Repair.

BACKGROUND: The goal of zone II flexor tendon surgery is to perform a repair with sufficient strength to withstand the forces encountered during rehabilitation. Postoperative rerupture and adhesion formation may lead to reoperation. This study aimed to determine the factors associated with reoperation after primary zone II flexor tendon repair. METHODS: In this retrospective case series, a total of 252 fingers in 201 patients underwent zone II flexor tendon repair. A medical record review was performed to collect data regarding patient demographics, injury and treatment characteristics and postoperative complications including reoperation. Reoperation was defined as any unplanned surgical procedure performed after initial flexor tendon repair. RESULTS: There were 49 fingers (19%) in 42 patients that underwent reoperation at a median of 5.5 (interquartile range: 2.8-7.9) months. Older age, workers' compensation, and a Kessler-type repair of the flexor digitorum profundus were independently associated with reoperation. CONCLUSIONS: In vitro studies suggest that Kessler-type repairs are inferior compared with other suture configurations. Our study demonstrates a clinical correlation to these biomechanical studies. Our results suggest that Kessler-type repairs are inferior compared with non-Kessler-type repairs, due to postoperative complications requiring secondary surgeries.

Role of tumor microenvironment in cancer progression and therapeutic strategy.

Cancer is now considered a tumor microenvironment (TME) disease, although it was originally thought to be a cell and gene expression disorder. Over the past 20 years, significant advances have been made in understanding the complexity of the TME and its impact on responses to various anticancer therapies, including immunotherapies. Cancer immunotherapy can recognize and kill cancer cells by regulating the body's immune system. It has achieved good therapeutic effects in various solid tumors and hematological malignancies. Recently, blocking of programmed death-1 (PD-1), programmed death-1 ligand-1 (PD-L1), and programmed death Ligand-2 (PD-L2), the construction of antigen chimeric T cells (CAR-T) and tumor vaccines have become popular immunotherapies Tumorigenesis, progression, and metastasis are closely related to TME. Therefore, we review the characteristics of various cells and molecules in the TME, the interaction between PD-1 and TME, and promising cancer immunotherapy therapeutics.