Integrating novel agents into the treatment of advanced mycosis fungoides and Sézary syndrome.

Agents targeting the unique biology of mycosis fungoides and Sézary syndrome are quickly being incorporated into clinical management. With these new therapies, we are now capable of inducing more durable responses and even complete remissions in advanced disease, outcomes which were exceedingly rare with prior therapies. Yet, even this new generation of therapies typically produce objective responses in only a minority of patients. As our therapeutic options increase, we are now challenged with selecting treatments from a growing list of options. To gain the full benefit of these novel agents, we must develop strategies to match treatments for the patients most likely to benefit from them. Here, we consider both the current approaches to treatment selection based on clinical features and the future of molecular biomarker-guided therapy for patients with this heterogeneous disease.

The Arabidopsis cyclophilin CYP18-1 facilitates PRP18 dephosphorylation and the splicing of introns retained under heat stress.

In plants, heat stress induces changes in alternative splicing, including intron retention; these events can rapidly alter proteins or downregulate protein activity, producing nonfunctional isoforms or inducing nonsense-mediated decay of messenger RNA (mRNA). Nuclear cyclophilins (CYPs) are accessory proteins in the spliceosome complexes of multicellular eukaryotes. However, whether plant CYPs are involved in pre-mRNA splicing remain unknown. Here, we found that Arabidopsis thaliana CYP18-1 is necessary for the efficient removal of introns that are retained in response to heat stress during germination. CYP18-1 interacts with Step II splicing factors (PRP18a, PRP22, and SWELLMAP1) and associates with the U2 and U5 small nuclear RNAs in response to heat stress. CYP18-1 binds to phospho-PRP18a, and increasing concentrations of CYP18-1 are associated with increasing dephosphorylation of PRP18a. Furthermore, interaction and protoplast transfection assays revealed that CYP18-1 and the PP2A-type phosphatase PP2A B'η co-regulate PRP18a dephosphorylation. RNA-seq and RT-qPCR analysis confirmed that CYP18-1 is essential for splicing introns that are retained under heat stress. Overall, we reveal the mechanism of action by which CYP18-1 activates the dephosphorylation of PRP18 and show that CYP18-1 is crucial for the efficient splicing of retained introns and rapid responses to heat stress in plants.

Taurodeoxycholate, a GPCR19 agonist, ameliorates atopic dermatitis in Balb/c mice.

Keratinocytes are pivotal cells in the pathogenesis of atopic dermatitis (AD) as much as Th2 cells. In this sense, regulation of pro-inflammatory features of keratinocytes might be useful for AD patients. P2X7R-mediated activation of NLRP3 inflammasome (N3I) in keratinocytes and myeloid cells plays crucial roles in AD. Nonetheless, inhibition of P2X7R has not been feasible because of polymorphisms and ubiquitous expression of P2X7R. Here, we report that GPCR19 colocalizes with P2X7R, and a GPCR19 agonist (taurodeoxycholate [TDCA]) inhibits the activation of P2X7R. Noncistronically, TDCA inhibits NF-kB activation via the adenylate cyclase-PKA pathway and BzATP-mediated Ca++ mobilization. Cistronically, TDCA suppresses the expression of P2X7R and N3I components in keratinocytes. NLRP3 oligomerization and the production of mature IL-1ß and IL-18 was suppressed by TDCA treatment in keratinocytes. Topical TDCA treatment ameliorates proinflammatory features of AD in mice induced by DNCB, MC903, or oxazolone. Taken together, a GPCR19 agonist such as TDCA might inhibit P2X7R-mediated N3I activation of keratinocytes, which is crucial for the pathogenesis of AD.

LiF-Rich Solid Electrolyte Interphase Formation by Establishing Sacrificial Layer on the Separator.

The formation of a stable solid electrolyte interphase (SEI) layer is crucial for enhancing the safety and lifespan of Li metal batteries. Fundamentally, a homogeneous Li+ behavior by controlling the chemical reaction at the anode/electrolyte interface is the key to establishing a stable SEI layer. However, due to the highly reactive nature of Li metal anodes (LMAs), controlling the movement of Li+ at the anode/electrolyte interface remains challenging. Here, an advanced approach is proposed for coating a sacrificial layer called fluorinated self-assembled monolayer (FSL) on a boehmite-coated polyethylene (BPE) separator to form a stable SEI layer. By leveraging the strong affinity between the fluorine functional group and Li+, the rapid formation of a LiF-rich SEI layer in the cell production and early cycling stage is facilitated. This initial stable SEI formation promotes the subsequent homogeneous Li+ flux, thereby improving the LMA stability and yielding an enhanced battery lifespan. Further, the mechanism behind the stable SEI layer generation by controlling the Li+ dynamics through the FSL-treated BPE separator is comprehensively verified. Overall, this research offers significant contributions to the energy storage field by addressing challenges associated with LMAs, thus highlighting the importance of interfacial control in achieving a stable SEI layer.

The rice NUCLEAR FACTOR-YA5 and MICRORNA169a module promotes nitrogen utilization during nitrogen deficiency.

Nitrogen (N) is essential for plant growth and development. Therefore, understanding its utilization is essential for improving crop productivity. However, much remains to be learned about plant N sensing and signaling. Here, rice (Oryza sativa) NUCLEAR FACTOR-YA5 (OsNF-YA5) expression was tightly regulated by N status and induced under N-deficient conditions. Overexpression (OE) of OsNF-YA5 in rice resulted in increased chlorophyll levels and delayed senescence compared to control plants under normal N conditions. Agronomic traits were significantly improved in OE plants and impaired in knockout mutants under N-deficient conditions. Using a dexamethasone-inducible system, we identified the putative targets of OsNF-YA5 that include amino acid, nitrate/peptide transporters, and NITRATE TRANSPORTER 1.1A (OsNRT1.1A), which functions as a key transporter in rice. OsNF-YA5 directly enhanced OsNRT1.1A expression and N uptake rate under N-deficient conditions. Besides, overexpression of OsNF-YA5 also enhanced the expression of GLUTAMINE SYNTHETASE 1/2 (GS1/2) and GLUTAMINE OXOGLUTARATE AMINOTRANSFERASE 1/2 (GOGAT1/2), increasing free amino acid contents under N-deficient conditions. Osa-miR169a expression showed an opposite pattern with OsNF-YA5 depending on N status. Further analysis revealed that osa-miR169a negatively regulates OsNF-YA5 expression and N utilization, demonstrating that an OsNF-YA5/osa-miR169a module tightly regulates rice N utilization for adaptation to N status.

DROUGHT-INDUCED BRANCHED-CHAIN AMINO ACID AMINOTRANSFERASE enhances drought tolerance in rice.

Plants accumulate several metabolites in response to drought stress, including branched-chain amino acids (BCAAs). However, the roles of BCAAs in plant drought responses and the underlying molecular mechanisms for BCAA accumulation remain elusive. Here, we demonstrate that rice (Oryza sativa) DROUGHT-INDUCED BRANCHED-CHAIN AMINO ACID AMINOTRANSFERASE (OsDIAT) mediates the accumulation of BCAAs in rice in response to drought stress. An in vitro enzyme activity assay indicated that OsDIAT is a branched-chain amino acid aminotransferase, and subcellular localization analysis revealed that OsDIAT localizes to the cytoplasm. The expression of OsDIAT was induced in plants upon exposure to abiotic stress. OsDIAT-overexpressing (OsDIATOX) plants were more tolerant to drought stress, whereas osdiat plants were more susceptible to drought stress compared with nontransgenic (NT) plants. Amino acid analysis revealed that BCAA levels were higher in OsDIATOX but lower in osdiat compared with in NT plants. Finally, the exogenous application of BCAAs improved plant tolerance to osmotic stress compared with that in control plants. Collectively, these findings suggest that OsDIAT mediates drought tolerance by promoting the accumulation of BCAAs.

Resistance to mogamulizumab is associated with loss of CCR4 in cutaneous T-cell lymphoma.

Mogamulizumab is a humanized anti-CC chemokine receptor 4 (CCR4) antibody approved for the treatment of mycosis fungoides and Sézary syndrome. Despite almost universal expression of CCR4 in these diseases, most patients eventually develop resistance to mogamulizumab. We tested whether resistance to mogamulizumab is associated with loss of CCR4 expression. We identified 17 patients with mycosis fungoides or Sézary syndrome who either were intrinsically resistant or acquired resistance to mogamulizumab. Low expression of CCR4 by immunohistochemistry or flow cytometry was found in 65% of patients. Novel emergent CCR4 mutations targeting the N-terminal and transmembrane domains were found in 3 patients after disease progression. Emerging CCR4 copy number loss was detected in 2 patients with CCR4 mutations. Acquisition of CCR4 genomic alterations corresponded with loss of CCR4 antigen expression. We also report on outcomes of 3 cutaneous T-cell lymphoma (CTCL) patients with gain-of-function CCR4 mutations treated with mogamulizumab. Our study indicates that resistance to mogamulizumab in CTCL frequently involves loss of CCR4 expression and emergence of CCR4 genomic alterations. This finding has implications for management and monitoring of CTCL patients on mogamulizumab and development of future CCR4-directed therapies.

Primary cutaneous lymphoma: recommendations for clinical trial design and staging update from the ISCL, USCLC, and EORTC.

The number of patients with primary cutaneous lymphoma (PCL) relative to other non-Hodgkin lymphomas (NHLs) is small and the number of subtypes large. Although clinical trial guidelines have been published for mycosis fungoides/Sézary syndrome, the most common type of PCL, none exist for the other PCLs. In addition, staging of the PCLs has been evolving based on new data on potential prognostic factors, diagnosis, and assessment methods of both skin and extracutaneous disease and a desire to align the latter with the Lugano guidelines for all NHLs. The International Society for Cutaneous Lymphomas (ISCL), the United States Cutaneous LymphomaConsortium (USCLC), and the Cutaneous Lymphoma Task Force of the European Organization for the Research and Treatment of Cancer (EORTC) now propose updated staging and guidelines for the study design, assessment, endpoints, and response criteria in clinical trials for all the PCLs in alignment with that of the Lugano guidelines. These recommendations provide standardized methodology that should facilitate planning and regulatory approval of new treatments for these lymphomas worldwide, encourage cooperative investigator-initiated trials, and help to assess the comparative efficacy of therapeutic agents tested across sites and studies.

Identifying and addressing unmet clinical needs in primary cutaneous B-cell lymphoma: A consensus-based paper from an ad-hoc international panel.

Primary cutaneous B-cell lymphomas (PCBCLs) are lymphoproliferative disorders that appear on the skin without evidence of extracutaneous manifestations at the time of diagnosis. There is a lack of evidence-based guidelines for their clinical management due to the availability of very few large scale studies and controlled clinical trials. Here we present and discuss a series of major unmet clinical needs (UCNs) in the management of PCBCLs by a panel of 16 experts involved in research and clinical practice of PCBCL. The Panel produced recommendations on the appropriateness of the clinical decisions concerning the identified clinical needs and proposed research for improving the knowledge needed to solve them. Recommendations and proposals were achieved by multiple-step formalized procedures to reach a consensus after a comprehensive analysis of the scientific literature. Recommendations and proposals lay in the domain of classification uncertainties of PCBCL, optimization of diagnosis, optimization of prognosis, optimization of staging and critical issues on therapeutic strategies with particular focus on new treatments. These recommendations are intended for use not only by experts but above all by dermatologists and hematologists with limited experience in the field of PCBCLs as well as general practitioners.

Comparison of Modified Shock Index and Shock Index for Predicting Massive Transfusion in Women with Primary Postpartum Hemorrhage: A Retrospective Study.

BACKGROUND The modified shock index (MSI) is calculated as the ratio of heart rate (HR) to mean arterial pressure (MAP) and has been used to predict the need for massive transfusion (MT) in trauma patients. This retrospective study from a single center aimed to compare the MSI with the traditional shock index (SI) to predict the need for MT in 612 women diagnosed with primary postpartum hemorrhage (PPH) at the Emergency Department (ED) between January 2004 and August 2023. MATERIAL AND METHODS The patients were divided into the MT group and the non-MT group. The predictive power of MSI and SI was compared using the areas under the receiver operating characteristic curve (AUC). The sensitivity, specificity, positive predictive value (PPV), and negative predictive value were calculated. RESULTS Out of 612 patients, 105 (17.2%) required MT. The MT group had higher median values than the non-MT group for MSI (1.58 vs 1.07, P<0.001) and SI (1.22 vs 0.80, P<0.001). The AUC for MSI, with a value of 0.811 (95% confidence interval [CI], 0.778-0.841), did not demonstrate a significant difference compared to the AUC for SI, which was 0.829 (95% CI, 0.797-0.858) (P=0.066). The optimal cutoff values for MSI and SI were 1.34 and 1.07, respectively. The specificity and PPV for MT were 77.1% and 40.2% for MSI, and 83.2% and 45.9% for SI. CONCLUSIONS Both MSI and SI were effective in predicting MT in patients with primary PPH. However, MSI did not demonstrate superior performance to SI.

Respiratory rate­oxygenation (ROX) index for predicting high-flow nasal cannula failure in patients with and without COVID-19.

BACKGROUND: The predictive value of the respiratory rate­oxygenation (ROX) index for a high-flow nasal cannula (HFNC) in patients with COVID-19 with acute hypoxemic respiratory failure (AHRF) may differ from patients without COVID-19 with AHRF, but these patients have not yet been compared. We compared the diagnostic accuracy of the ROX index for HFNC failure in patients with AHRF with and without COVID-19 during acute emergency department (ED) visits. METHODS: We performed a retrospective analysis of patients with AHRF treated with an HFNC in an ED between October 2020 and April 2022. The ROX index was calculated at 1, 2, 4, 6, 12, and 24 h after HFNC placement. The primary outcome was the failure of the HFNC, which was defined as the need for subsequent intubation or death within 72 h. A receiver operating characteristic (ROC) curve was used to evaluate discriminative power of the ROX index for HFNC failure. RESULTS: Among 448 patients with AHRF treated with an HFNC in an ED, 78 (17.4%) patients were confirmed to have COVID-19. There was no significant difference in the HFNC failure rates between the non-COVID-19 and COVID-19 groups (29.5% vs. 33.3%, p = 0.498). The median ROX index was higher in the non-COVID-19 group than in the COVID-19 group at all time points. The prognostic power of the ROX index for HFNC failure as evaluated by the area under the ROC curve was generally higher in the COVID-19 group (0.73-0.83) than the non-COVID-19 group (0.62-0.75). The timing of the highest prognostic value of the ROX index for HFNC failure was at 4 h for the non-COVID-19 group, whereas in the COVID-19 group, its performance remained consistent from 1 h to 6 h. The optimal cutoff values were 6.48 and 5.79 for the non-COVID-19 and COVID-19 groups, respectively. CONCLUSIONS: The ROX index had an acceptable discriminative power for predicting HFNC failure in patients with AHRF with and without COVID-19 in the ED. However, the higher ROX index thresholds than those in previous publications involving intensive care unit (ICU) patients suggest the need for careful monitoring and establishment of a new threshold for patients admitted outside the ICU.

Outcomes and Complications of Sole Reconstruction Using Lateral Thoracic Free Tissue Transfer.

BACKGROUND: The complex structure of the sole of the foot makes the repair of extensive defects challenging. The present study, therefore, aimed to address a gap in current research by evaluating the potential of the lateral thoracic free flap, including perforator options and chimeric configurations, to be used as an advanced solution for comprehensive sole reconstruction. PATIENTS AND METHODS: We retrospectively collected the following data from the charts of patients with sole defects, due to various causes, who underwent lateral thoracic free tissue transfers: patient demographics; etiologies; comorbidities; flap types and dimensions; pedicle length; operative time; follow-up period; complications; and management. RESULTS: The present study included 54 patients who underwent lateral thoracic free tissue transfer, citing infection, trauma, tumor, and posttraumatic sequelae as the major etiologies. We used the following techniques for the reconstruction of sole defects: thoracodorsal artery perforator free flap (83.3%); latissimus dorsi musculocutaneous free flap (1.9%); and various chimeric pattern flaps (14.8%). Free tissue transfer in the lateral thoracic region offers versatility for reconstruction, as well as low donor site morbidity. Complications observed in the present study included wound dehiscence (9.3%), partial necrosis (9.3%), and pressure ulcers (22.2%), although most patients healed favorably without flap loss. CONCLUSIONS: The lateral thoracic free flap is a viable option for the reconstruction of the sole of the foot and allows for the effective reconstruction of complex defects. It contains a sustainable skin paddle, and multiple components can be easily included as a chimeric type. Further studies should seek to identify ways to prevent pressure ulcers, which was the only known long-term complication in the present study.

Analysis of Operation Duration in Thoracodorsal Artery Perforator Free-Flap Surgery of the Lower Extremities.

PURPOSE: This retrospective study aimed to identify the factors that affect the duration of thoracodorsal artery perforator (TDAP) free-flap surgery and to offer strategies for optimizing the surgical procedure. METHODS: We analyzed 80 TDAP flap surgeries performed by a single surgeon between January 2020 and December 2022, specifically focusing on free flaps used for lower-extremity defects with single-artery and single-vein anastomosis. The operation duration was defined as the time between the surgeon's initial incision and completion of reconstruction. Linear regression analyses were conducted to identify the factors affecting operation duration. RESULTS: The average operative duration was 149 minutes (range, 80-245 minutes). All flaps survived, although 8 patients experienced partial flap loss. The operative duration decreased with increasing patient age and when end-to-end arterial anastomosis was performed. However, the risk increased with larger flap sizes and in patients with end-stage renal disease. CONCLUSIONS: Our study identified several factors and methods that could accelerate TDAP free-flap procedures. These findings offer valuable insights for optimizing surgical processes and improving overall surgical outcomes. Although further research is needed to confirm and expand upon these findings, our study provides important guidance for surgeons in developing effective strategies for TDAP flap surgery.

Assessing the Role of Yarn Placement in Plated Knit Strain Sensors: A Detailed Study of Their Electromechanical Properties and Applicability in Bending Cycle Monitoring.

In this study, we explore how the strategic positioning of conductive yarns influences the performance of plated knit strain sensors fabricated using commercial knitting machines with both conductive and non-conductive yarns. Our study reveals that sensors with conductive yarns located at the rear, referred to as 'purl plated sensors', exhibit superior performance in comparison to those with conductive yarns at the front, or 'knit plated sensors'. Specifically, purl plated sensors demonstrate a higher sensitivity, evidenced by a gauge factor ranging from 3 to 18, and a minimized strain delay, indicated by a 1% strain in their electromechanical response. To elucidate the mechanisms behind these observations, we developed an equivalent circuit model. This model examines the role of contact resistance within varying yarn configurations on the sensors' sensitivity, highlighting the critical influence of contact resistance in conductive yarns subjected to wale-wise stretching on sensor responsiveness. Furthermore, our findings illustrate that the purl plated sensors benefit from the vertical movement of non-conductive yarns, which promotes enhanced contact between adjacent conductive yarns, thereby improving both the stability and sensitivity of the sensors. The practicality of these sensors is confirmed through bending cycle tests with an in situ monitoring system, showcasing the purl plated sensors' exceptional reproducibility, with a standard deviation of 0.015 across 1000 cycles, and their superior sensitivity, making them ideal for wearable devices designed for real-time joint movement monitoring. This research highlights the critical importance of conductive yarn placement in sensor efficacy, providing valuable guidance for crafting advanced textile-based strain sensors.

The Correlates of Collective and Individual Trauma on Mental Health Outcomes Among Afghan Refugees: A Study of Sociodemographic Differences.

Following the U.S. military's departure from Afghanistan, a significant number of Afghan refugees have resettled in the United States, presenting complex mental health challenges exacerbated by extensive traumatic exposure. This demographic is particularly affected by collective trauma due to war, genocide, and the loss of homeland. However, detailed investigations into the correlations between collective trauma and mental health outcomes among Afghan refugees are limited. This study sought to explore the relationship between collective trauma and mental health outcomes within the Afghan refugee population in the United States, paying particular attention to the influence of sociodemographic factors. Identifying subgroups at greater risk allows for the development of more targeted mental health interventions. The study surveyed 173 Afghan refugees employing snowball sampling, utilizing a cross-sectional design. Data collection was facilitated through online and in-person surveys in English, Dari, and Pashto. Key measures included the Harvard Trauma Questionnaire for individual trauma experiences, the Historical Loss Scale for collective trauma, the Historical Loss Associated Symptoms Scale for collective trauma symptoms, the Afghan Symptom Checklist-22 for mental health symptoms, and the Post-Migration Living Difficulties Scale for post-migration stressors. Statistical analyses involved Pearson's correlation for variable associations, with nonparametric Mann-Whitney U and Kruskal-Wallis tests conducted to assess sociodemographic impacts due to data's non-normal distribution. The analysis revealed significant variations in collective trauma and mental health outcomes across subgroups. Afghan women, minoritized ethnic groups, those who experienced extended displacement, and refugees with uncertain visa statuses reported higher collective trauma levels and worse mental health outcomes. Statistical significance was noted in the correlations between collective trauma and mental health symptoms (r = .53, p < .01) and between post-migration difficulties and mental health (r = .33, p < .01). The disparities in mental health outcomes based on sociodemographic characteristics were significant, with nonparametric tests showing clear distinctions across different groups (Kruskal-Wallis H = 14.76, p < .05 for trauma experience by visa status). This study emphasizes the critical need for mental health interventions that account for the complex experiences of collective trauma among Afghan refugees, especially among identified subgroups. Tailoring mental health services to address the specific needs highlighted through disaggregated data can enhance support for Afghan refugees in the United States. This research contributes to a deeper understanding of the relationship between collective trauma and refugee mental health, advocating for nuanced care strategies in resettlement environments.

Surface Oxygen Vacancy Inducing Li-Ion-Conducting Percolation Network in Composite Solid Electrolytes for All-Solid-State Lithium-Metal Batteries.

Composite solid electrolytes (CSEs) are newly emerging components for all-solid-state Li-metal batteries owing to their excellent processability and compatibility with the electrodes. Moreover, the ionic conductivity of the CSEs is one order of magnitude higher than the solid polymer electrolytes (SPEs) by incorporation of inorganic fillers into SPEs. However, their advancement has come to a standstill owing to unclear Li-ion conduction mechanism and pathway. Herein, the dominating effect of the oxygen vacancy (Ovac ) in the inorganic filler on the ionic conductivity of CSEs is demonstrated via Li-ion-conducting percolation network model. Based on density functional theory, indium tin oxide nanoparticles (ITO NPs) are selected as inorganic filler to determine the effect of Ovac on the ionic conductivity of the CSEs. Owing to the fast Li-ion conduction through the Ovac inducing percolation network on ITO NP-polymer interface, LiFePO4 /CSE/Li cells using CSEs exhibit a remarkable capacity in long-term cycling (154 mAh g-1 at 0.5C after 700 cycles). Moreover, by modifying the Ovac concentration of ITO NPs via UV-ozone oxygen-vacancy modification, the ionic conductivity dependence of the CSEs on the surface Ovac from the inorganic filler is directly verified.

Self-Formation of a Ru/ZnO Multifunctional Bilayer for the Next-Generation Interconnect Technology via Area-Selective Atomic Layer Deposition.

This study suggests a Ru/ZnO bilayer grown using area-selective atomic layer deposition (AS-ALD) as a multifunctional layer for advanced Cu metallization. As a diffusion barrier and glue layer, ZnO is selectively grown on SiO2 , excluding Cu, where Ru, as a liner and seed layer, is grown on both surfaces. Dodecanethiol (DDT) is used as an inhibitor for the AS-ALD of ZnO using diethylzinc and H2 O at 120 °C. H2 plasma treatment removes the DDT adsorbed on Cu, forming inhibitor-free surfaces. The ALD-Ru film is then successfully deposited at 220 °C using tricarbonyl(trimethylenemethane)ruthenium and O2 . The Cu/bilayer/Si structural and electrical properties are investigated to determine the diffusion barrier performance of the bilayer film. Copper silicide is not formed without the conductivity degradation of the Cu/bilayer/Si structure, even after annealing at 700 °C. The effect of ZnO on the Ru/SiO2 structure interfacial adhesion energy is investigated using a double-cantilever-beam test and is found to increase with ZnO between Ru and SiO2 . Consequently, the Ru/ZnO bilayer can be a multifunctional layer for advanced Cu interconnects. Additionally, the formation of a bottomless barrier by eliminating ZnO on the via bottom, or Cu, is expected to decrease the via resistance for the ever-shrinking Cu lines.

Radiation Therapy for Primary Cutaneous Gamma Delta Lymphoma Prior to Stem Cell Transplantation.

We present a patient with widespread PCGD-TCL of the bilateral arms and legs, who underwent radiotherapy with 34 Gy in 17 fractions using circumferential VMAT and 3-D printed bolus to the four extremities prior to planned stem cell transplant, who was then found to have progression in the liver, lung, and skin, followed by drastic regression of all in and out-of-field lesions on imaging 1.5 months later. The cause of regression may be related to a radiation-induced abscopal effect from the immunomodulatory effects of radiation, or related to immune reactivation in the setting of cessation of systemic immunosuppressive agents.

Enhancing the interferon-γ release assay through omission of nil and mitogen values.

PURPOSE: To address the limited utility of the interferon (IFN)-γ release assay (IGRA) caused by its variability and inconsistency. METHODS: This retrospective cohort study was based on data obtained between 2011 and 2019. QuantiFERON-TB Gold-In-Tube was used to measure IFN-γ levels in nil, tuberculosis (TB) antigen, and mitogen tubes. RESULTS: Of 9,378 cases, 431 had active TB. The non-TB group comprised 1,513 IGRA-positive, 7,202 IGRA-negative, and 232 IGRA-indeterminate cases. Nil-tube IFN-γ levels were significantly higher in the active TB group (median = 0.18 IU/mL; interquartile range: 0.09-0.45 IU/mL) than in the IGRA-positive non-TB (0.11 IU/mL; 0.06-0.23 IU/mL) and IGRA-negative non-TB (0.09 IU/mL; 0.05-0.15 IU/mL) groups (P < 0.0001). From receiver operating characteristic analysis, TB antigen tube IFN-γ levels had higher diagnostic utility for active TB than TB antigen minus nil values. In a logistic regression analysis, active TB was the main driver of higher nil values. In the active TB group, after reclassifying the results based on a TB antigen tube IFN-γ level of 0.48 IU/mL, 14/36 cases with negative results and 15/19 cases with indeterminate results became positive, while 1/376 cases with positive results became negative. Overall, the sensitivity for detecting active TB improved from 87.2 to 93.7%. CONCLUSION: The results of our comprehensive assessment can aid in IGRA interpretation. Since nil values are governed by TB infection rather than reflecting background noise, TB antigen tube IFN-γ levels should be used without subtracting nil values. Despite indeterminate results, TB antigen tube IFN-γ levels can be informative.

Diabetic foot resurfacing using microvascular tissue transfer from lateral thoracic region.

AIMS: Diabetic foot ulcer is a major complication of diabetes mellitus and amputation is often needed. Since mortality rate after amputation is comparatively high, saving diabetic foot is required not only for preserving function and life quality, but also for decreasing mortality rate. This study was designed to analyse experience of limb salvage in patients with diabetic foot using free flaps from the lateral thoracic region over a 10-year period. MATERIALS AND METHODS: Between 2009 and 2018, 297 cases of diabetic foot underwent surgical procedures. We analysed the 83 cases who underwent free flap from lateral thoracic region. Patient data were reviewed retrospectively. RESULTS: A total of 83 patients, 56 of them males, were included in this study. Age of patients ranged from 27 to 80 years. Twenty patients underwent percutaneous transluminal angioplasty procedures. The latissimus dorsi muscle sparing technique was used in 7 cases. A thoracodorsal artery perforator flap was used in 68 cases. A thoracodorsal artery perforator chimaeric flap was performed in 8 cases. The flap survival rate was 98.8% and the limb salvage rate was 96.4%. The mean follow-up was 6.5 years. During follow-up 14 patients suffered recurrence of foot ulcers. CONCLUSIONS: Ten-year experience of using flaps from the lateral thoracic region revealed superior outcomes in terms of flap survival and limb saving compared to those in a recent meta-analysis and other reports. Long vascular pedicle technique and the chimaeric technique might be the alternative methods for multiple or vascular insufficient diabetic foot defects.