Interferon-γ induces combined pyroptotic angiopathy and APOL1 expression in human kidney disease.

Elevated interferon (IFN) signaling is associated with kidney diseases including COVID-19, HIV, and apolipoprotein-L1 (APOL1) nephropathy, but whether IFNs directly contribute to nephrotoxicity remains unclear. Using human kidney organoids, primary endothelial cells, and patient samples, we demonstrate that IFN-γ induces pyroptotic angiopathy in combination with APOL1 expression. Single-cell RNA sequencing, immunoblotting, and quantitative fluorescence-based assays reveal that IFN-γ-mediated expression of APOL1 is accompanied by pyroptotic endothelial network degradation in organoids. Pharmacological blockade of IFN-γ signaling inhibits APOL1 expression, prevents upregulation of pyroptosis-associated genes, and rescues vascular networks. Multiomic analyses in patients with COVID-19, proteinuric kidney disease, and collapsing glomerulopathy similarly demonstrate increased IFN signaling and pyroptosis-associated gene expression correlating with accelerated renal disease progression. Our results reveal that IFN-γ signaling simultaneously induces endothelial injury and primes renal cells for pyroptosis, suggesting a combinatorial mechanism for APOL1-mediated collapsing glomerulopathy, which can be targeted therapeutically.

Salvage radiofrequency ablation followed by external beam radiotherapy for inoperable recurrent differentiated thyroid cancer.

PURPOSE: The treatment of recurrent thyroid cancer with critical organ invasion is challenging. The combination of radiofrequency ablation (RFA) and external beam radiation therapy (EBRT) has been proposed as an effective option. This study evaluates outcomes for inoperable residual/recurrent differentiated thyroid cancer (rDTC) patients treated with RFA followed by EBRT. MATERIALS AND METHODS: Patients with rDTC treated with RFA followed by EBRT were retrospectively studied. RFA was performed using a free-hand, 'moving-shot' technique under US or CT guidance. For lesions invading critical structures intolerant to 'en bloc' high-temperature RFA, limited-field EBRT using 6- or 10-MV photons was used for adjuvant treatment at a dose of 66 Gy in 33 daily fractions. Toxicities and outcomes were reviewed. RESULTS: Between April 2020 and January 2022, 11 patients with 14 rDTC lesions underwent RFA followed by EBRT. Five patients had metastatic lesions at rDTC diagnosis. With a median follow-up period of 33.7 months, all patients maintained locoregional control, while achieving a 2-year survival rate of 90.9%. This combined treatment achieved a volume reduction ratio of 92.1% ± 5.1%. The mean nadir thyroglobulin level in patients without initial distant metastases after treatment was 1.40 ± 0.81 ng/ml. Regarding treatment-related complications, one patient (9%) experienced temporary hoarseness after RFA, grade 2 radiation dermatitis occurred in 3 patients (27.2%), and grade 2 dysphagia was noted in 4 patients (36.4%). No grade 3 or greater toxicities occurred. CONCLUSIONS: Salvage RFA followed by EBRT is feasible, effective and safe for patients with rDTC.

Comparison of contraction-type and noncontraction-type lymphatic vessels in lymphaticovenous anastomosis for cancer-related unilateral lower limb lymphedema: a retrospective cohort propensity-score-matched outcome analysis.

BACKGROUND: Contraction-type lymphatic vessels (LV) are considered suboptimal for lymphaticovenous anastomosis (LVA). However, despite these pathological changes, their functionality and link to outcomes have not been fully elucidated. The aim of this study was to determine the impact on outcomes when contraction-type LVs were used for LVA compared to the noncontraction-type (normal + ectatic) counterpart for treating lower limb lymphedema. STUDY DESIGN: Eighty-three patients with gynecologic cancer-related unilateral lower-limb lymphedema who underwent LVA as their primary treatment were enrolled in this study. The study group included 20 patients who used only contraction-type LVs. An additional 63 patients (control group) received noncontraction-type LVs only. Patients with a history of LVA, liposuction, or excisional therapy were excluded. Patient characteristics, intraoperative findings, functional parameters, and pre-LVA and post-LVA volume changes were recorded and matched using propensity scores. The primary endpoint was the volume change at 6/12 months after LVA. RESULTS: After matching, 20 patients were included in each group. All parameters were matched, except that the study group still had a significantly inferior indocyanine green (ICG)-positive ratio, lymph flow-positive ratio, and washout-positive ratios ( P <0.001, P =0.003, and P <0.001, respectively) when compared to the control group after matching. However, at 1-year follow-up, the postoperative percentage volume reduction was comparable between the groups ( P= 0.619). CONCLUSION: The use of contraction-type LVs for LVA is encouraged when no other LVs are available.

Lymphatic-based Lymphosome: A Novel Hypothesis with Clinical Implication for Supermicrosurgical Lymphaticovenous Anastomosis.

Understanding the anatomical territories drained by lymphatic vessels (LVs) is essential for a better comprehension of lymphatic anatomy and functionality, and for performing lymphatic procedures such as lymphaticovenous anastomosis (LVA). However, current concepts regarding the lymphatic territory are insufficient to explain some of the clinical observations. As shown in the figures, within one incision for the LVA, one to two lymphatic vessels (LV) remained unenhanced on indocyanine green (ICG) lymphography, whereas the rest of the LVs were enhanced. To answer this question, one must examine the concept of the lymphosome, first described by Suami, defined as a particular region drained by LVs into the same subgroup of regional lymph nodes (LNs) (eg, superficial groin LNs). Suami's lymphosome concept represents "LN-based lymphosomes." In addition, Shinaoka identified four distinct lymphatic groups (anteromedial, anterolateral, posteromedial, and posterolateral) in the lower limbs after ICG injection. This represents the concept "group-based lymphosomes." Nevertheless, neither the LN- nor group-based lymphosome concepts offer an appropriate explanation for the clinical findings described above. In addition to the aforementioned lymphosome concepts, the author proposes a novel hypothesis called "lymphatic-based lymphosome," which considers each LV as a single lymphosome. Therefore, the normal-type LV remained unenhanced when ICG was not injected into the draining territory. To enhance post-LVA outcomes, an even distribution of anastomoses to different group-based lymphosomes is important, as is avoiding performing all anastomoses onto a single LV or within the same group-based lymphosome.

Density Spectral Array Enables Precise Sedation Control for Supermicrosurgical Lymphaticovenous Anastomosis: A Retrospective Observational Cohort Study.

Supermicrosurgical lymphaticovenous anastomosis (LVA) is a minimally invasive surgical technique that creates bypasses between lymphatic vessels and veins, thereby improving lymphatic drainage and reducing lymphedema. This retrospective single-center study included 137 patients who underwent non-intubated LVA in southern Taiwan. A total of 119 patients were enrolled and assigned to two study groups: the geriatric (age ≥ 75 years, n = 23) and non-geriatric groups (age < 75 years, n = 96). The primary outcome was to investigate and compare the arousal and maintenance of the propofol effect-site concentration (Ce) using an electroencephalographic density spectral array (EEG DSA) in both groups. The results showed that the geriatric group required less propofol (4.05 [3.73-4.77] mg/kg/h vs. 5.01 [4.34-5.92] mg/kg/h, p = 0.001) and alfentanil (4.67 [2.53-5.82] µg/kg/h vs. 6.68 [3.85-8.77] µg/kg/h, p = 0.047). The median arousal Ce of propofol among the geriatric group (0.6 [0.5-0.7] µg/mL) was significantly lower than that in patients aged ≤ 54 years (1.3 [1.2-1.4] µg/mL, p < 0.001), 55-64 years (0.9 [0.8-1.0] µg/mL, p < 0.001), and <75 years (0.9 [0.8-1.2] µg/mL, p < 0.001). In summary, the combined use of EEG DSA provides the objective and depth of adequate sedation for extensive non-intubated anesthesia in late-elderly patients who undergo LVA without perioperative complications.

Analgesic and Anesthetic Efficacy of Rocuronium/Sugammadex in Otorhinolaryngologic Surgery: A Propensity Score-Matched Analysis.

The use of rocuronium/sugammadex in otorhinolaryngologic surgery improves intubation conditions and surgical rating scales. This study primarily aimed to evaluate the effect of the combination of rocuronium and sugammadex on intraoperative anesthetic consumption. The secondary outcomes were the intraoperative and postoperative morphine milligram equivalent (MME) consumption, duration of intraoperative hypertension, extubation time, incidence of delayed extubation and postoperative nausea and vomiting, pain score, and length of stay. A total of 2848 patients underwent otorhinolaryngologic surgery at a tertiary medical center in southern Taiwan. After applying the exclusion criteria, 2648 of these cases were included, with 167 and 2481 in the rocuronium/sugammadex and cisatracurium/neostigmine groups, respectively. To reduce potential bias, 119 patients in each group were matched by propensity scores for sex, age, body weight, and type of surgery. We found that the rocuronium/sugammadex group was associated with significant preservation of the intraoperative sevoflurane and MME consumption, with reductions of 14.2% (p = 0.009) and 11.8% (p = 0.035), respectively. The use of the combination of rocuronium and sugammadex also significantly increased the dose of intraoperative labetalol (p = 0.002), although there was no significant difference in intraoperative hypertensive events between both groups. In conclusion, our results may encourage the use of the combination of rocuronium and sugammadex as part of volatile-sparing and opioid-sparing anesthesia in otorhinolaryngologic surgery.

Management of difficult hepatic artery reconstructions to reduce complications through continual technical refinements in living donor liver transplantations.

BACKGROUND: Hepatic artery reconstruction (HAR) for liver transplantation is crucial for successful outcomes. We evaluated transplantation outcome improvement through continual technical refinements. MATERIALS AND METHODS: HAR was performed in 1448 living donor liver transplants by a single plastic surgeon from 2008 to 2020. Difficult HARs were defined as graft or recipient hepatic artery ≤2 mm, size discrepancy (≥2 to 1), multiple hepatic arteries, suboptimal quality, intimal dissection of graft or recipient hepatic artery (HA), and immediate redo during transplantation. Technique refinements include early vessel injury recognition, precise HA dissection, the use of clips to ligate branches, an oblique cut for all HARs, a modified funneling method for size discrepancy, liberal use of an alternative artery to replace a pathologic HA, and reconstruction of a second HA for grafts with dual hepatic arteries in the graft. RESULTS: Difficult HARs were small HA (21.35%), size discrepancy (12.57%), multiple hepatic arteries (11.28%), suboptimal quality (31.1%), intimal dissection (20.5%), and immediate redo (5.18%). The overall hepatic artery thrombosis (HAT) rate was 3.04% in this series. The average HAT rate during the last 4 years (2017-2020) was 1.46% (6/408), which was significantly lower than the average HAT rate from 2008 to 2016 (39/1040, 3.8%) with a statistical significance (p = 0.025). Treatment for posttransplant HAT included anastomosis after trim back (9), reconstruction using alternatives (19), and nonsurgical treatment with urokinase (9). CONCLUSION: Careful examination of the HA under surgical microscope and selection of the appropriate recipient HA are key to successful reconstruction. Through continual technical refinements, we can reduce HA complications to the lowest degree.

Effect of Lymphaticovenous Anastomosis on Muscle Edema, Limb, and Subfascial Volume in Lower Limb Lymphedema: MRI Studies.

BACKGROUND: Although satisfactory volume reduction in secondary unilateral lower limb lymphedema after lymphaticovenous anastomosis (LVA) in the affected limb has been well reported, alleviation of muscle edema and the impact of LVA on the contralateral limb have not been investigated. STUDY DESIGN: This retrospective cohort study enrolled patients who underwent supermicrosurgical LVA between November 2015 and January 2017. Pre- and post-LVA muscle edema were assessed using fractional anisotropy (FA) and apparent diffusion coefficient (ADC). The primary endpoint was changes in limb/subfascial volume assessed with magnetic resonance volumetry at least 6 months after LVA. RESULTS: Twenty-one patients were enrolled in this study. Significant percentage reductions in post-LVA muscle edema were found in the affected thigh (83.6% [interquartile range = range of Q1 to Q3; 29.8-137.1] [FA], 53.3% [27.0-78.4] [ADC]) as well as limb (21.7% [4.4-26.5]) and subfascial (18.7% [10.7-39.1]) volumes. Similar findings were noted in the affected lower leg: 71.8% [44.0-100.1] (FA), 59.1% [45.8-91.2] (ADC), 21.2% [6.8-38.2], and 28.2% [8.5-44.8], respectively (all p < 0.001). Significant alleviation of muscle edema was also evident in the contralateral limbs (thigh: 25.1% [20.4-57.5] [FA]; 10.7% [6.6-17.7] [ADC]; lower leg: 47.1% [35.0-62.8] [FA]; 14.6% [6.5-22.1] [ADC]; both p < 0.001), despite no statistically significant difference in limb and subfascial volumes. CONCLUSIONS: Our study found significant reductions in muscle edema and limb/subfascial volumes in the affected limb after LVA. Our findings regarding edema in the contralateral limb were consistent with possible lymphedema-associated systemic influence on the unaffected limb, which could be surgically relieved.

Lymphaticovenous Anastomosis for Treating Secondary Lower Limb Lymphedema in Older Patients-A Retrospective Cohort Study.

Despite an increased incidence of secondary lower limb lymphedema (LLL) and severity of comorbidities with age, the impact of age on the effectiveness of lymphaticovenous anastomosis (LVA) in the older patients remains unclear. Methods: This retrospective cohort study enrolled older patients (age > 65 years) with secondary unilateral LLL. All patients underwent supermicrosurgical LVA. Demographic data and intraoperative findings including lymphatic vessel (LV) diameter, LV functionality (indocyanine green-enhanced and Flow positivity), and lymphosclerosis classification were recorded. Magnetic resonance volumetry was used for measuring preoperative and postoperative volume changes at 6 months and one year after LVA as primary and secondary endpoints. Results: Thirty-two patients (29 females/3 males) with a median age of 71.0 years [range, 68.0 to 76.3] were enrolled. The median duration of lymphedema was 6.4 [1.0 to 11.7] years. The median LV diameter was 0.7 [0.5 to 0.8] mm. The percentage of ICG-enhanced and Flow-positive LVs were 89.5% and 85.8%, respectively. The total percentage of suitable LVs (s0 and s1) for LVA based on lymphosclerosis classification was 75.9%. There were significant six-month and one-year post-LVA percentage volume reductions compared to pre-LVA volume (both p < 0.001). A significant reduction in cellulitis incidence was also noted after LVA (p < 0.001). No surgical or postoperative complications were found. Conclusion: Relief of secondary LLL was achievable through LVA in older patients who still possessed favorable LV characteristics, including larger LV diameters as well as a high proportion of functional LVs with a low grade of lymphosclerosis.

Impact of retrograde anastomosis during supermicrosurgical lymphaticovenous anastomosis for cancer-related lower limb lymphedema: A retrospective cohort propensity-score-matched outcome analysis.

BACKGROUND: In addition to antegrade anastomosis, retrograde anastomosis has been thought to offer further improvements after lymphaticovenous anastomosis (LVA) by bypassing the retrograde lymphatic flow. However, this concept has yet to be validated. The aim of this study was to determine the impacts on outcomes of performing both retrograde and antegrade anastomosis, as compared to antegrade-only anastomosis for treating lower limb lymphedema. STUDY DESIGN: This was a retrospective cohort propensity score-matched study. Eighty-seven patients with gynecologic cancer-related lower limb lymphedema were enrolled, including 58 patients who had received both antegrade and retrograde anastomoses (Group I) and 29 patients who had received antegrade-only anastomoses (Group II) as the control group. LVA was the primary treatment. Patients who had previous LVA, liposuction, or excisional therapy were excluded. Patient characteristics, intraoperative findings, and functional parameters including the ratio of indocyanine green-enhanced and flow-positive lymphatic vessels were recorded. Magnetic resonance volumetry was used for outcome assessments. The primary endpoint was the volume change at 6 months after LVA. RESULTS: After matching, a total of 26 patients have remained in each group. All parameters were matched except that Group I still had significantly more median LVA performed compared to Group II (8 [IQR: 5.3-10.0] vs. 5.5 [4.3-6.0], p = 0.001, respectively). Group II showed more post-LVA improvements at six-month and one-year follow-up compared to Group I but without statistically significant differences. CONCLUSION: The use of supplementary retrograde anastomoses is discouraged since it may lead to inferior post-LVA outcome compared to antegrade-only anastomoses.

Cannabinoid receptor 1 antagonist genistein attenuates marijuana-induced vascular inflammation.

Epidemiological studies reveal that marijuana increases the risk of cardiovascular disease (CVD); however, little is known about the mechanism. Δ9-tetrahydrocannabinol (Δ9-THC), the psychoactive component of marijuana, binds to cannabinoid receptor 1 (CB1/CNR1) in the vasculature and is implicated in CVD. A UK Biobank analysis found that cannabis was an risk factor for CVD. We found that marijuana smoking activated inflammatory cytokines implicated in CVD. In silico virtual screening identified genistein, a soybean isoflavone, as a putative CB1 antagonist. Human-induced pluripotent stem cell-derived endothelial cells were used to model Δ9-THC-induced inflammation and oxidative stress via NF-κB signaling. Knockdown of the CB1 receptor with siRNA, CRISPR interference, and genistein attenuated the effects of Δ9-THC. In mice, genistein blocked Δ9-THC-induced endothelial dysfunction in wire myograph, reduced atherosclerotic plaque, and had minimal penetration of the central nervous system. Genistein is a CB1 antagonist that attenuates Δ9-THC-induced atherosclerosis.

Use of Microscope-Integrated Near-Infrared Fluorescence for Enhancing Deep Lymphatic Vessel Detection during Supermicrosurgical Lymphaticovenous Anastomosis: A Longitudinal Cohort Study.

BACKGROUND: The default setting of microscope-integrated near-infrared fluorescence (MINIRF) using indocyanine green for locating superficial lymphatic vessels during lymphaticovenous anastomosis was limited to less than or equal to 70 percent intensity. The authors investigated whether maximizing the MINIRF intensity setting could increase the number of deep lymphatic vessels being found, thereby increasing the total number of lymphatic vessels for lymphaticovenous anastomosis. METHODS: This longitudinal cohort study enrolled 94 patients (86 female and eight male patients) with lower limb lymphedema. Superficial lymphatic vessels were identified with the MINIRF default setting, before maximal intensity was used for deep lymphatic vessel detection. Primary/secondary endpoints included the number of superficial and deep lymphatic vessels identified. No control was used. Demographic data, intraoperative findings [including superficial and deep (indocyanine green-enhanced and non-indocyanine green-enhanced) lymphatic vessels], and severity of lymphosclerosis were recorded. Data in three regions of the lower limb (i.e., foot/above ankle, below knee, and thigh) were compared. RESULTS: A total of 481 lymphatic vessels were identified, comprising 260 superficial and 221 deep lymphatic vessels. The median number of lymphatic vessels found per patient was five (interquartile range, four to six), and the median lymphatic vessel size was 0.63 mm (interquartile range, 0.5 to 0.8 mm). No difference was found in number (p = 0.360), size (p = 0.215), or severity of lymphosclerosis (p = 0.226) between the overall superficial and deep lymphatic vessels in the three lower limb regions. CONCLUSIONS: Deep lymphatic vessel detection can be aided by maximizing MINIRF intensity. These deep lymphatic vessels are comparable to superficial lymphatic vessels in number, size, and functionality, making them potentially valuable for lymphedema improvement. CLINICAL QUESTION/LEVEL OF EVIDENCE: Diagnostic, II.

Recovery of Dysregulated Genes in Cancer-Related Lower Limb Lymphedema After Supermicrosurgical Lymphaticovenous Anastomosis - A Prospective Longitudinal Cohort Study.

PURPOSE: This study aims at profiling the expression of dysregulated genes in circulating monocytes of patients with cancer-related lower limb lymphedema before and after treatment with supermicrosurgical lymphaticovenous anastomosis (LVA). MATERIALS AND METHODS: This prospective longitudinal cohort study enrolled 51 women with post-treatment gynecological cancer, including those with unilateral lymphedema (study group, n = 25) and those without (control group, n = 26). Venous blood samples obtained from the study group before and after LVA and those from the controls were sent for next-generation sequencing, which was validated by real-time PCR. Dysregulated gene expression in the study group, relative to expression in the controls, was recorded before LVA. After one month, postoperative changes in the expression of the identified genes were evaluated. Protein-protein interaction (PPI) was used to investigate dysregulated genes whose expression returned to baseline levels after LVA. RESULTS: Of the 148 preoperative dysregulated genes, which comprised 108 up- and 40 down-regulated genes, 78 genes, consisting of 69 up- and 9 down-regulated genes, showed post-LVA recovery to baseline levels. Through PPI analysis, five functional modules involving immunity, lipid metabolism, oxidative stress, transcriptional regulators, and tumor suppression, as well as six hub genes (CCL2, LPL, PDK4, FOXO3, EGR1, and DUSP5), were identified. Cross-linking and co-regulated genes between modules were also identified. CONCLUSION: Localized lymphedema leads to dysregulated gene expression in circulating monocytes. The current study is the first to identify the hub genes related to lymphedema and demonstrate the recovery of some dysregulated genes after LVA.

Recipient Venule Selection and Anastomosis Configuration for Lymphaticovenular Anastomosis in Extremity Lymphedema: Algorithm Based on 1,000 Lymphaticovenular Anastomosis.

BACKGROUND: The lymphaticovenular anastomosis (LVA) has three components, lymphatics, venules, and anastomosis, and all of them influence the anastomotic pressure gradient. Although it has been demonstrated that venule flow dynamics has an independent impact on the outcomes regardless the degeneration status of lymphatic vessels, recipient venules (RV) have been mainly neglected in literature. METHODS: From January 2016 to February 2020, 232 nonconsecutive patients affected by extremity lymphedema underwent LVA, for a total of 1,000 LVAs. Only patients with normal-to-ectasic lymphatic collectors were included to focus the evaluation on the RV only. The preoperative collected data included the location, diameter, and continence of the selected venules, the expected number, the anastomoses configuration, and their flow dynamics according to BSO classification. RESULTS: The 232 patients included 117 upper limb lymphedema (ULL) and 115 lower limb lymphedema (LLL). The average size of RV was 0.81 ± 0.32 mm in end-to-end (E-E), 114 ± 0.17 mm in end-to-side (E-S), 0.39 ± 0.22 mm in side-to-end (S-E), and 0.76 ± 0.38 mm in side-to-side (S-S) anastomoses. According to the BSO classification, on a total of 732 RV, 105(14%) were backflow venules, 136 (19%) were slack, and 491 (67%) were outlet venules. Also, 824 (82%) were E-E, 107 (11%) were E-S, 51 (5%) were S-E, and 18 (2%) were S-S anastomoses. CONCLUSION: Based on 1,000 LVAs with similar lymphatic characteristics, we propose our algorithm that may aid the lymphatic microsurgeon in the selection of RV and the consequent anastomosis configuration, in order of obtain the best flow dynamic through the LVA. This therapeutic study reflects level of evidence IV.

Selection of Optimal Functional Lymphatic Vessel Cutoff Size in Supermicrosurgical Lymphaticovenous Anastomosis in Lower Extremity Lymphedema.

BACKGROUND: Functional lymphatic vessels are essential for supermicrosurgical lymphaticovenous anastomosis. Theoretically, the larger the lymphatic vessel, the better the flow. However, large lymphatic vessels are not readily available. Since the introduction of lymphaticovenous anastomosis, no guidelines have been set as to how small a lymphatic vessel is still worthwhile for anastomosis. METHODS: In this longitudinal cohort study, unilateral lower limb lymphedema patients who underwent lymphaticovenous anastomosis between March of 2016 and January of 2019 were included. Demographic data and intraoperative findings including the number and size of lymphatic vessels were recorded. The cutoff size was determined by receiver operating characteristic curve analysis, based on the functional properties of lymphatic vessels. Clinical correlation was made with post-lymphaticovenous anastomosis volume measured by magnetic resonance volumetry. RESULTS: A total of 141 consecutive patients (124 women and 17 men) with a median age of 60.0 years (range, 56.7 to 61.2 years) were included. The cutoff size for a functional lymphatic vessel was determined to be 0.50 mm (i.e., lymphatic vessel0.5) from a total of 1048 lymphatic vessels. Significant differences were found between the number of lymphatic vessels0.5 anastomosed (zero to one, two to three, and greater than over equal to four lymphatic vessels0.5), the median post-lymphaticovenous anastomosis volume reduction (in milliliters) (p < 0.001), and the median percentage volume reduction (p = 0.012). CONCLUSIONS: Lymphatic vessel0.5 can be a valuable reference for lymphaticovenous anastomosis. Post-lymphaticovenous anastomosis outcome can be enhanced with the use of lymphatic vessel0.5 for anastomoses. CLINICAL QUESTION/LEVEL OF EVIDENCE: Risk, II.

Endocardial/endothelial angiocrines regulate cardiomyocyte development and maturation and induce features of ventricular non-compaction.

AIMS: Non-compaction cardiomyopathy is a devastating genetic disease caused by insufficient consolidation of ventricular wall muscle that can result in inadequate cardiac performance. Despite being the third most common cardiomyopathy, the mechanisms underlying the disease, including the cell types involved, are poorly understood. We have previously shown that endothelial cell-specific deletion of the chromatin remodeller gene Ino80 results in defective coronary vessel development that leads to ventricular non-compaction in embryonic mouse hearts. We aimed to identify candidate angiocrines expressed by endocardial and endothelial cells (ECs) in wildtype and LVNC conditions in Tie2Cre;Ino80fl/fltransgenic embryonic mouse hearts, and test the effect of these candidates on cardiomyocyte proliferation and maturation. METHODS AND RESULTS: We used single-cell RNA-sequencing to characterize endothelial and endocardial defects in Ino80-deficient hearts. We observed a pathological endocardial cell population in the non-compacted hearts and identified multiple dysregulated angiocrine factors that dramatically affected cardiomyocyte behaviour. We identified Col15a1 as a coronary vessel-secreted angiocrine factor, downregulated by Ino80-deficiency, that functioned to promote cardiomyocyte proliferation. Furthermore, mutant endocardial and endothelial cells up-regulated expression of secreted factors, such as Tgfbi, Igfbp3, Isg15, and Adm, which decreased cardiomyocyte proliferation and increased maturation. CONCLUSIONS: These findings support a model where coronary endothelial cells normally promote myocardial compaction through secreted factors, but that endocardial and endothelial cells can secrete factors that contribute to non-compaction under pathological conditions.

Is There an Optimal Timing of Adductor Canal Block for Total Knee Arthroplasty?-A Retrospective Cohort Study.

Adductor canal block (ACB) has gained popularity for postoperative pain control after total knee arthroplasty (TKA). However, its role in TKA has been questioned recently. Our study aimed to clarify the role of ACB in reducing postoperative pain after TKA and to elucidate an optimal timing to perform ACB for better outcomes. We conducted a comprehensive review of the perioperative records of 652 patients undergoing primary TKA from January 2019 to December 2019. Patients were divided into three groups: Group A received general anesthesia without ACB, Group B received ACB before inducing general anesthesia, and Group C received ACB at the post-anesthesia recovery unit (PACU). Patients in Groups B and C had lower pain visual analogue scale (VAS) scores than patients in Group A at the PACU. Opioid consumption was similar among the three groups; however, a slightly higher dose was required by Group A patients. Higher VAS scores were recorded in the ward in Group A than in Groups B and C with the leg at rest. In addition, higher VAS scores were recorded in Group A than in Groups B and C with the leg in continuous passive motion (CPM) training. More patients in Group A (34.9%) quit their first CPM training after a few cycles than those in Groups B (27.0%) and C (20.1%). Group A patients required a higher per kg dose of opioids in the ward than Groups B and C patients. Additionally, the hourly consumption of sevoflurane was similar among the three groups of patients, while Group A and C patients required a higher hourly per kg dose of intraoperative opioids than Group B patients. More patients in Group A (67.6%) and C (61.7%) developed intraoperative hypertension than patients in Group B (52.7%). There was no significant difference in PON (postoperative nausea), POV (postoperative vomiting), postoperative dizziness, or patient satisfaction among the three groups of patients. Group A patients had a longer length of hospital stay compared to Group B and C patients. In conclusion, preoperative ACB could be a better choice for patients undergoing TKA as it decreases intraoperative opioid consumption and facilitates a stable hemodynamic state during surgery.

Lower Limb Lymphedema Patients Can Still Benefit from Supermicrosurgical Lymphaticovenous Anastomosis (LVA) after Vascularized Lymph Node Flap Transfer (VLNT) as Delayed Lymphatic Reconstruction-A Retrospective Cohort Study.

BACKGROUND: For lymphedema patients who received a vascularized lymph node flap transfer (VLNT) as their primary treatment, what are the treatment options when they seek further improvement? With recent publications supporting the use of lymphaticovenous anastomosis (LVA) for treating severe lymphedema, we examined whether LVA could benefit post-VLNT patients seeking further improvement. METHODS: This retrospective cohort study enrolled eight lymphedema patients with nine lymphedematous limbs (one patient suffered from bilateral lower limb lymphedema) who had received VLNT as their primary surgery. Patients with previous LVA, liposuction, excisional therapy, or incomplete data were excluded. LVA was performed on nine lower lymphedematous limbs. Demographic data and intraoperative findings were recorded. Preoperative and postoperative limb volumes were measured with magnetic resonance volumetry. The primary outcome was the limb volume measured 6 months post-LVA. RESULTS: The median duration of lymphedema before LVA was 10.5 (4.9-15.3) years. The median waiting time between VLNT and LVA was 41.4 (22.3-97.9) months. The median volume gained in the lymphedematous limb was 3836 (2505-4584) milliliters (mL). The median post-LVA follow-up period was 18 (6-30) months. Significant 6-month and 1-year post-LVA percentage volume reductions were found compared to pre-LVA volume (both p < 0.001). CONCLUSION: Based on the results from this study, the authors recommend the use of LVA as a secondary procedure for post-VLNT patients seeking further improvement.