The small screw-apex distance is potentially associated with femoral head osteonecrosis in adults with femoral neck fractures treated by closed reduction and percutaneous 3 parallel cannulated screws.

OBJECTIVE: Femoral neck fractures (FNFs) are among the most common fractures in elderly individuals. Surgery is the main treatment for FNFs, and osteonecrosis of the femoral head (ONFH) is one of the unacceptable complications. This study aimed to assess both the clinical and radiological outcomes in patients with FNFs treated with three parallel cannulated screws and to identify relationship between screws position and ONFH. PATIENTS AND METHODS: A total of 100 patients who were treated with closed reduction and fixed with 3 parallel cannulated screws met the inclusion criteria between January 2014 and December 2020 at authors' institution. The follow-up duration, age, sex, affected side, and injury-to-surgery interval were collected; the neck-shaft angle of both hips, screw-apex distance (SAD) and the tip-apex distance (TAD)were measured; and the Garden classification, quality of reduction and presence of ONFH were evaluated. RESULTS: The sample consisted of 37 males and 63 females, with 60 left and 40 right hips affected. The mean age of patients was 54.93 ± 12.24 years, and the mean follow-up was 56.3 ± 13.38 months. The overall incidence of ONFH was 13%. No significant difference was observed in the incidence of ONFH by affected side, age, fracture displacement, injury-to-surgery interval, neck-shaft angle deviation, or reduction quality. The SAD was significantly shorter in ONFH patients than in normal patients for all three screws (p = 0.02, 0.02, and 0.01, respectively). CONCLUSIONS: The short SAD of all screws is associated with femoral head necrosis of FNFs treated with 3 cannulated screws. The short SAD indicated that screws malpositioning in the weight-bearing area of the femoral head, potentially harming the blood supply and compromising the anchorage of the primary compressive trabeculae in this region.

A new classification for surgical NEC during exploratory laparotomy: introduction and reproducibility assessment.

PURPOSE: Variability in necrosis patterns and operative techniques in surgical necrotizing enterocolitis (NEC) necessitates a standardized classification system for consistent assessment and comparison. This study introduces a novel intraoperative reporting system for surgical NEC, focusing on reliability and reproducibility. METHODS: Analyzing surgical NEC cases from January 2018 to June 2023 at two tertiary neonatal and pediatric surgery units, a new classification system incorporating anatomical details and intestinal involvement extent was developed. Its reproducibility was quantified using kappa coefficients (κ) for interobserver and intraobserver reliability, assessed by four specialists. Furthermore, following surgery, the occurrence of mortality and enteric autonomy were evaluated on the basis of surgical decision-making of the novel intraoperative classification system for surgical NEC. RESULTS: In total, 95 patients with surgical NEC were included in this analysis. The mean κ value of the intra-observer reliability was 0.889 (range, 0.790-0.941) for the new classification, indicating excellent agreement and the inter-observer reliability was 0.806 (range, 0.718-0.883), indicating substantial agreement. CONCLUSION: The introduced classification system for surgical NEC shows high reliability, deepening the understanding of NEC's intraoperative exploration aspects. It promises to indicate operative strategies, enhance prognosis prediction, and substantially facilitate scholarly communication in pediatric surgery. Importantly, it explores the potential for a standardized report and may represent a step forward in classifying surgical NEC, if pediatric surgeons are open to change.

Portal vein gas is a sign of intestinal necrosis after pesticide poisoning: a case report.

Portal vein gas accumulation and intestinal pneumatosis are uncommon signs indicating a high mortality risk in cases of intestinal ischemic necrosis. However, the widespread use of computed tomography has led to an increase in detection of benign lesions. We report a case of portal vein gas accumulation resulting from organophosphorus pesticide poisoning. A male patient was brought to the hospital in a comatose state with bilateral pupils that measured 1.0 mm, and he showed shortness of breath and wet rattles in the lungs. A cholinesterase concentration of 214 U/L was detected on an auxiliary examination. The patient was diagnosed with organophosphorus pesticide poisoning and underwent mechanical ventilation, hemoperfusion, and continuous renal replacement therapy according to the poisoning guidelines. On the fifth day, considerable abdominal distension was observed. An abdominal computed tomography scan revealed dilation of the small bowel and ascending colon with fluid and gas accumulation, as well as gas within the intestinal wall and hepatic veins. Although portal vein gas and intestinal pneumatosis are a sign of mortality requiring immediate surgical intervention, an increasing number of benign cases suggests potential benefits of conservative treatment approaches.

Clinicopathological Significance of Tumor Budding in Breast Carcinoma.

BACKGROUND: Tumour budding Tuberculosis is a new prognostic marker whose role in breast cancer is still under evaluation. Our aim was to study Tuberculosis in breast carcinoma and correlate it with other prognostic markers. METHODS: A descriptive cross-sectional study was conducted over 2 years on 75 invasive breast carcinoma specimens and biopsies. Hematoxylin and Eosin sections were examined for tumour grade, stage, molecular subtype, necrosis, lymphovascular invasion inflammation and counting of Tuberculosis. Lymph node metastasis was studied only in mastectomies. TB was defined as a cluster of 1-5 tumour cells and counted in 10 consecutive 400X fields. The cut-off for high grade TB was taken as ?10 per 10 HPFs. Immunohistochemical staining was done for molecular subtyping and differentiating Tuberculosis from mimickers. Statistical analysis was done using chi square test and Fischer's exact test. RESULTS: Tuberculosis was present in 66/75 cases; 53% (n=35) were high grade. Among these, majority were of T2 (74%, n= 26), grade 2 (52%, n= 18), luminal A (34%, n= 12), had 3+ inflammation (46%, n= 16) and peripheral tumour buds (54%). Necrosis and lymphovascular invasion were absent in 77% and 71%, respectively. Lymph node metastasis was seen in 63% (n= 25/28) cases. Statistically significant association (p= 0.016) was observed between degree of inflammation and Tuberculosis grade. However, no significant association was observed between TB and other prognostic markers of breast carcinoma. CONCLUSIONS: In our study, association of Tuberculosis with different prognostic markers was appreciated but was not statistically significant. However, it highlights need for standardization of Tuberculosis reporting.

Mitochondrial Permeability Transition, Cell Death and Neurodegeneration.

Neurodegenerative diseases are chronic conditions occurring when neurons die in specific brain regions that lead to loss of movement or cognitive functions. Despite the progress in understanding the mechanisms of this pathology, currently no cure exists to treat these types of diseases: for some of them the only help is alleviating the associated symptoms. Mitochondrial dysfunction has been shown to be involved in the pathogenesis of most the neurodegenerative disorders. The fast and transient permeability of mitochondria (the mitochondrial permeability transition, mPT) has been shown to be an initial step in the mechanism of apoptotic and necrotic cell death, which acts as a regulator of tissue regeneration for postmitotic neurons as it leads to the irreparable loss of cells and cell function. In this study, we review the role of the mitochondrial permeability transition in neuronal death in major neurodegenerative diseases, covering the inductors of mPTP opening in neurons, including the major ones-free radicals and calcium-and we discuss perspectives and difficulties in the development of a neuroprotective strategy based on the inhibition of mPTP in neurodegenerative disorders.

Galectin-3 and Autophagy in Renal Acute Tubular Necrosis.

Acute kidney injury (AKI) is a public health burden with increasing morbidity and mortality rates and health care costs. Acute tubular necrosis (ATN) is the most common cause of AKI. Cisplatin (CIS) is a platinum-based chemotherapeutic agent used in the treatment of a wide variety of malignancies such as lung, breast, ovary, testis, bladder, cervix, and head and neck cancers. Autophagy plays an important role in AKI. Galectin-3 (Gal-3) is significantly increased in renal tubules in AKI; however, its role in autophagy is not well understood. Male C57B6/J and B6.Cg-Lgals3 /J Gal-3 knockout (KO) mice were used to induce AKI using a CIS mouse model of ATN. Renal Gal-3 and autophagy proteins' expression were measured using standard histologic, immunofluorescent, and enzyme-linked immunosorbent assay techniques. The data were presented as the mean ± S.E. Statistically significant differences (p < 0.05) were calculated between experimental groups and corresponding control groups by one-way analysis of variance. There was a significant increase in renal concentrations of Gal-3 in the Gal-3 wild-type CIS-treated mice when compared with sham control mice. There were significantly higher concentrations of renal LC3B, ATG13, Ulk-1, Beclin, ATG5, ATG12, ATG9A, and p-AMPK in the CIS-treated Gal-3 KO mice than in the Gal-3 wild-type CIS-treated mice. Further, there were significantly higher concentrations of mTOR, p- NF-κB, beta-catenin, and p62 in the kidneys of the Gal-3 wild-type CIS-treated mice than in the Gal-3 KO CIS-treated mice. Our findings affirm the connection between Gal-3 and autophagy, revealing its central role as a connector with prosurvival signaling proteins. Gal-3 plays a pivotal role in orchestrating cellular responses by interacting with prosurvival signal pathways and engaging with autophagy proteins. Notably, our observations highlight that the absence of Gal-3 can enhance autophagy in CIS-induced ATN.

IL-10 and TGF-ß1 may weaken the efficacy of preoperative anti-tuberculosis therapy in older patients with spinal tuberculosis.

Spinal tuberculosis is a common extrapulmonary type that is often secondary to pulmonary or systemic infections. Mycobacterium tuberculosis infection often leads to the balance of immune control and bacterial persistence. In this study, 64 patients were enrolled and the clinicopathological and immunological characteristics of different age groups were analyzed. Anatomically, spinal tuberculosis in each group mostly occurred in the thoracic and lumbar vertebrae. Imaging before preoperative anti-tuberculosis therapy showed that the proportion of abscesses in the older group was significantly lower than that in the younger and middle-aged groups. However, pathological examination of surgical specimens showed that the proportion of abscesses in the older group was significantly higher than that in the other groups, and there was no difference in the granulomatous inflammation, caseous necrosis, inflammatory necrosis, acute inflammation, exudation, granulation tissue formation, and fibrous tissue hyperplasia. B cell number was significantly lower in the middle-aged and older groups compared to the younger group, while the number of T cells, CD4+ T cells, CD8+ T cells, macrophages, lymphocytes, plasma cells, and NK cells did not differ. Meaningfully, we found that the proportion of IL-10 high expression and TGF-ß1 positive in the older group was significantly higher than that in the younger group. TNF-α, CD66b, IFN-γ, and IL-6 expressions were not different among the three groups. In conclusion, there are some differences in imaging, pathological, and immune features of spinal tuberculosis in different age groups. The high expression of IL-10 and TGF-ß1 in older patients may weaken their anti-tuberculosis immunity and treatment effectiveness.

Minimizing Nipple-Areolar Complex Complications in Prepectoral Breast Reconstruction After Nipple-Sparing Mastectomy.

PURPOSE: Nipple-areolar complex (NAC) viability remains a significant concern following prepectoral tissue expander (TE) reconstruction after nipple-sparing mastectomy (NSM). This study assesses the impact of intraoperative TE fill on NAC necrosis and identifies strategies for mitigating this risk. METHODS: A chart review of all consecutive, prepectoral TEs placed immediately after NSM was performed between March 2017 and December 2022 at a single center. Demographics, mastectomy weight, intraoperative TE fill, and complications were extracted for all patients. Partial NAC necrosis was defined as any thickness of skin loss including part of the NAC, whereas total NAC necrosis was defined as full-thickness skin loss involving the entirety of the NAC. P < 0.05 was considered statistically significant. RESULTS: Forty-six patients (83 breasts) with an average follow-up of 22 months were included. Women were on average 46 years old, nonsmoker (98%), and nondiabetic (100%) and had a body mass index of 23 kg/m2. All reconstructions were performed immediately following prophylactic mastectomies in 49% and therapeutic mastectomies in 51% of cases. Three breasts (4%) were radiated, and 15 patients (33%) received chemotherapy. Mean mastectomy weight was 346 ± 274 g, median intraoperative TE fill was 150 ± 225 mL, and median final TE fill was 350 ± 170 mL. Partial NAC necrosis occurred in 7 breasts (8%), and there were zero instances of complete NAC necrosis. On univariate analysis, partial NAC necrosis was not associated with any patient demographic or operative characteristics, including intraoperative TE fill. In multivariable models controlling for age, body mass index, mastectomy weight, prior breast surgery, and intraoperative TE fill, partial NAC necrosis was associated with lower body mass index (odds ratio, 0.53; confidence interval [CI], 0.29-0.98; P < 0.05) and higher mastectomy weight (odds ratio, 1.1; CI, 1.01-1.20; P < 0.05). Prior breast surgery approached significance, as those breasts had a 19.4 times higher odds of partial NAC necrosis (95% CI, 0.88-427.6; P = 0.06). CONCLUSIONS: Nipple-areolar complex necrosis following prepectoral TE reconstruction is a rare but serious complication. In this study of 83 breasts, 7 (8%) developed partial NAC necrosis, and all but one were able to be salvaged.

Granulomatous Myocarditis Caused by Candida Spp Infection in a Spontaneously Diabetic Torii Rat.

Background: Myocarditis refers to myocardial inflammation with necrosis caused by non-infectious of infectious agents such as bacteria, fungi, or drugs. Candida is known to cause myocarditis in healthy and immunocompromised individuals. Diabetes mellitus causes chronic hyperglycemia due to impaired secretion or hypofunction of insulin, induces a compromised state, and increases the risk of contracting various infections. Objective: We report a case of granulomatous myocarditis caused by Candida in a Spontaneously Diabetic Torii rat, a non-obese diabetic model. Case report: A male SDT rat, 61 weeks of age, was housed in conventional environment. The rat was provided a commercial diet and tap water ad libitum. The heart was sampled and prepared the specimen of hematoxylin-and-eosin-, Sirius-red-, Giemsa-, Grocott-stain. Histologically, formation of large granulation tissue was observed in the left ventricular wall. A center of the foci showed necrosis. Moreover, inflammatory cells infiltration and fibrous component were increased surrounding the foci and between myocardial cells. A Grocott and Giemsa staining-positive cell masses occasionally appearing in the foci were considered to be Candida because of their characteristic form. Conclusion: The development and progression of myocarditis were potentially related to a diabetes-induced compromised state.

Retroperitoneal Laparoscopic Debridement and Drainage for Pancreatic Abscess.

In patients with severe necrotizing pancreatitis, pancreatic necrosis and secondary infection of surrounding tissues can quickly spread to the whole retroperitoneal space. Treatment of pancreatic abscess complicating necrotizing pancreatitis is difficult and has a high mortality rate. The well-accepted treatment strategy is early debridement of necrotic tissues, drainage, and postoperative continuous retroperitoneal lavage. However, traditional open surgery has several disadvantages, such as severe trauma, interference with abdominal organs, a high rate of postoperative infection and adhesion, and hardness with repeated debridement. The retroperitoneal laparoscopic approach has the advantages of minimal invasion, a better drainage route, convenient repeated debridement, and avoidance of the spread of retroperitoneal infection to the abdominal cavity. In addition, retroperitoneal drainage leads to fewer drainage tube problems, including miscounting, displacement, or siphon. The debridement and drainage of pancreatic abscess tissue via the retroperitoneal laparoscopic approach plays an increasingly irreplaceable role in improving patient prognosis and saving healthcare resources and costs. The main procedures described here include laying the patient on the right side, raising the lumbar bridge and then arranging the trocar; establishing the pneumoperitoneum and cleaning the pararenal fat tissues; opening the lateral pyramidal fascia and the perirenal fascia outside the peritoneal reflections; opening the anterior renal fascia and entering the anterior pararenal space from the rear; clearing the necrotic tissue and accumulating fluid; and placing drainage tubes and performing postoperative continuous retroperitoneal lavage.

Effect of 2-methoxyestradiol on mammary tumor initiation and progression.

BACKGROUND: The anti-cancer agent 2-methoxyestradiol (2-ME) has been shown to have anti-proliferative and anti-angiogenic properties. Previously, the effect of 2-ME on early- and late-stage breast cancer (BC) was investigated in vivo using a transgenic mouse model (FVB/N-Tg(MMTV-PyVT)) of spontaneous mammary carcinoma. Anti-tumor effects were observed in late-stage BC with no effect on early-stage BC. Given the contrasting results obtained from the different BC stages, we have now investigated the effect of 2-ME when administered before the appearance of palpable tumors. METHODS: Each mouse received 100 mg/kg 2-ME on day 30 after birth, twice per week for 28 days, while control mice received vehicle only. Animals were terminated on day 59. Lung and mammary tissue were obtained for immunohistochemical analysis of CD163 and CD3 expression, and histological examination was performed to analyze tumor necrosis. Additionally, blood samples were collected to measure plasma cytokine levels. RESULTS: 2-ME increased tumor mass when compared to the untreated animals (p = .0139). The pro-tumorigenic activity of 2-ME was accompanied by lower CD3+ T-cell numbers in the tumor microenvironment (TME) and high levels of the pro-inflammatory cytokine interleukin (IL)-1ß. Conversely, 2-ME-treatment resulted in fewer CD163+ cells detectable in the TME, increased levels of tumor necrosis, increased IL-10 plasma levels, and low IL-6 and IL-27 plasma levels. CONCLUSION: Taken together, these findings suggest that 2-ME promotes early-stage BC development.

Remotely Triggered LAD Occlusion Using a Balloon Catheter in Spontaneously Breathing Mice.

Acute myocardial infarction (AMI) is a prevalent and high-mortality cardiovascular condition. Despite advancements in revascularization strategies for AMI, it frequently leads to myocardial ischemia-reperfusion injury (IRI), amplifying cardiac damage. Murine models serve as vital tools for investigating both acute injury and chronic myocardial remodeling in vivo. This study presents a unique closed-chest technique for remotely inducing myocardial IRI in mice, enabling the investigation of the very early phase of occlusion and reperfusion using in-vivo imaging such as MRI or PET. The protocol utilizes a remote occlusion method, allowing precise control over ischemia initiation after chest closure. It reduces surgical trauma, enables spontaneous breathing, and enhances experimental consistency. What sets this technique apart is its potential for simultaneous noninvasive imaging, including ultrasound and magnetic resonance imaging (MRI), during occlusion and reperfusion events. It offers a unique opportunity to analyze tissue responses in almost real-time, providing critical insights into processes during ischemia and reperfusion. Extensive systematic testing of this innovative approach was conducted, measuring cardiac necrosis markers for infarction, assessing the area at risk using contrast-enhanced MRI, and staining infarcts at the scar maturation stage. Through these investigations, emphasis was placed on the value of the proposed tool in advancing research approaches to myocardial ischemia-reperfusion injury and accelerating the development of targeted interventions. Preliminary findings demonstrating the feasibility of combining the proposed innovative experimental protocol with noninvasive imaging techniques are presented herein. These initial results highlight the benefit of utilizing the purpose-built animal cradle to remotely induce myocardial ischemia while simultaneously conducting MRI scans.

Anti-tumor necrosis factor-α therapy may not be safe during pregnancy in women with inflammatory bowel disease: an updated meta-analysis and systematic review.

BACKGROUND: Inflammatory Bowel Disease (IBD) affects reproductive-aged women. Active disease can lead to decreased fertility. Although the vast majority of international guidelines recommend for the continuation of anti-TNF-α during pregnancy, recent studies have raised concerns about the safety of anti-tumor necrosis factor-α (TNF-α) therapy during pregnancy, both for patients and for physicians. METHODS: Studies that evaluate the safety of anti-TNF-α therapy in pregnant women with IBD were identified using bibliographical searches. An updated meta-analysis was performed for pregnancy outcomes, such as live birth, abortion, still birth, preterm birth, low birth weight, congenital abnormalities, and neonatal infection. Odds ratio (OR) with 95% confidence interval (CI) are reported. Data on disease activity, timing of anti-TNF-α therapy were collected for further analysis. RESULTS: Overall, 11 studies were screened from on-line databases and international meeting abstracts. An increased risk of abortion (OR, 1.33; 95% CI, 1.02-1.74; P = 0.04) and preterm birth (OR, 1.16; 95% CI, 1.05-1.28; P = 0.004), and a decreased risk of live birth (OR, 0.83; 95% CI, 0.74-0.94; P = 0.002]) were found in the anti-TNF-α therapy group compared with the control group (no use of anti-TNF-α therapy). The subgroup analyses based on the disease activity showed there is no significant association between the use of anti-TNF-α therapy during pregnancy on adverse pregnancy outcomes of abortion, preterm birth, and live birth. The rates of still birth, low birth weight, and congenital abnormalities in the anti-TNF-α therapy group were not significantly different from those in the control group. CONCLUSIONS: Anti-TNF-α therapy does not increase the risks of still birth, low birth weight, and congenital abnormalities; however it may be assicated with increased risks of abortion and preterm birth, which are accompanied by a lower rate of live birth. Although these findings may be confounding by potential disease activity, they offer some opposite viewpoints with biologic agent use. Therefore, more studies are required to further confirm the safety of anti-TNF-α therapy in pregnancy with IBD.

Scalp necrosis following preoperative endovascular embolisation of the superficial temporal artery for meningioma.

A woman in her late 50s with a left frontal lobe convexity meningioma underwent an elective endovascular embolisation of the left middle meningeal artery and distal branches of the left superficial temporal artery prior to surgical resection of the tumour. On postoperative day 46, she developed scalp necrosis, leading to poor wound healing requiring wound debridement and a complex plastic surgery reconstruction with a rotational flap. Endovascular embolisation of vascular tumours prior to surgical resection does not come without risks. The lack of consistency in the literature regarding indication, technique and outcomes makes it difficult to define the exact role of preoperative meningioma embolisation.

Immune-Mediated Necrotizing Myopathies: Current Landscape.

PURPOSE OF REVIEW: Immune-mediated necrotizing myopathy (IMNM), characterized by acute or subacute onset, severe weakness, and elevated creatine kinase levels, poses diagnostic and therapeutic challenges. This article provides a succinct overview of IMNM, including clinical features, diagnostic strategies, and treatment approaches. RECENT FINDINGS: Recent insights highlight the different clinical presentations and therapeutic options of IMNM stratified by autoantibody positivity and type. Additionally, recent findings call into question the reported link between statin use and IMNM. This review synthesizes current knowledge on IMNM, emphasizing its distinct clinical features and challenging management. The evolving understanding of IMNM underscores the need for a comprehensive diagnostic approach that utilizes a growing range of modalities. Early and aggressive immunomodulatory therapy remains pivotal. Ongoing research aims to refine diagnostic tools and therapeutic interventions for this challenging muscle disorder, underscoring the importance of advancing our understanding to enhance patient outcomes.

Genetic and morphological characterization of a new genotype of nervous necrosis virus circulating among Nile tilapia in the south of Egypt

Nervous necrosis virus (NNV) is the causative agent of viral nervous necrosis in freshwater and marine fishes. In this study, NNV circulating among wild and farmed Nile tilapia (Oreochromis niloticus) was genetically and morphologically characterized using reverse transcription polymerase chain reaction (RT-PCR), sequencing analysis, and transmission electron microscopy (TEM). Brain, eye, and other organ (spleen, kidney, heart, and liver) specimens were collected from 87 wild (66) and farmed (21) Nile tilapia fish during their adult or juvenile stage at different localities in Qena and Sohag governorates in southern Egypt. Among them, 57/87 fish showed suspected NNV clinical signs, and 30/87 were healthy. The results revealed that NNV was detected in 66 out of 87 fish (58.62% in the wild and 17.24% in farmed Nile tilapia by RT-PCR), and the prevalence was higher among diseased (55.17%) than in healthy (20.69%) fish. NNV was detected in the brain, eye, and other organs. Using TEM, virion size variations based on the infected organs were observed. Nucleotide sequence similarity indicated that NNVs had a divergence of 75% from other fish nodaviruses sequenced in Egypt and worldwide. Phylogenetic analysis distinguished them from other NNV genotypes, revealing the emergence of a new NNV genotype in southern Egypt. In conclusion, NNV is circulating among diseased and healthy Nile tilapia, and a new NNV genotype has emerged in southern Egypt. (AU)

Mono-quinoxaline-induced DNA structural alteration leads to ZBP1/RIP3/MLKL-driven necroptosis in cancer cells.

Evading the cellular apoptosis mechanism by modulating multiple pathways poses a sturdy barrier to effective chemotherapy. Cancer cell adeptly resists the apoptosis signaling pathway by regulating anti and pro-apoptotic proteins to escape cell death. Nevertheless, bypassing the apoptotic pathway through necroptosis, an alternative programmed cell death process, maybe a potential therapeutic modality for apoptosis-resistant cells. However, synthetic mono-quinoxaline-based intercalator-induced cellular necroptosis as an anti-cancer perspective remains under-explored. To address this concern, we undertook the design and synthesis of quinoxaline-based small molecules (3a-3l). Our approach involved enhancing the π-surface of the mandatory benzyl moiety to augment its ability to induce DNA structural alteration via intercalation, thereby promoting cytotoxicity across various cancer cell lines (HCT116, HT-29, and HeLa). Notably, the potent compound 3a demonstrated the capacity to induce DNA damage in cancer cells, leading to the induction of ZBP1-mediated necroptosis in the RIP3-expressed cell line (HT-29), where Z-VAD effectively blocked apoptosis-mediated cell death. Interestingly, we observed that 3a induced RIP3-driven necroptosis in combination with DNA hypomethylating agents, even in the RIP3-silenced cell lines (HeLa and HCT116). Overall, our synthesized compound 3a emerged as a promising candidate against various cancers, particularly in apoptosis-compromised cells, through the induction of necroptosis.

Nafamostat mesylate decreases skin flap necrosis in a mouse model of type 2 diabetes by protecting the endothelial glycocalyx.

The success rate of flap tissue reconstruction has increased in recent years owing to advancements in microsurgical techniques. However, complications, such as necrosis, are still more prevalent in diabetic patients compared to non-diabetic individuals, presenting an ongoing challenge. To address this issue, many previous studies have examined vascular anastomoses dilation and stability, primarily concerning surgical techniques or drugs. In contrast, in the present study, we focused on microvascular damage of the peripheral microvessels in patients with diabetes mellitus and the preventative impact of nafamostat mesylate. Herein, we aimed to investigate the effects of hyperglycemia on glycocalyx (GCX) levels in mice with type 2 diabetes. We examined the endothelial GCX (eGCX) in skin flap tissue of 9-12-week-old type 2 diabetic mice (db/db mice) using a perforator skin flap and explored treatment with nafamostat mesylate. The growth rates were compared after 1 week. Heterotype (db/+) mice were used as the control group. Morphological examination of postoperative tissues was performed at 1, 3, 5, and 7 days post-surgery. In addition, db/db mice were treated with 30 mg/kg/day of nafamostat mesylate daily and were evaluated on postoperative day 7. Seven days after surgery, all db/db mice showed significant partial flap necrosis. Temporal observation of the skin flaps revealed a stasis-like discoloration and necrosis starting from the contralateral side of the remaining perforating branch. The control group did not exhibit flap necrosis, and the flap remained intact. In the quantitative assessment of endothelial glycans using lectins, intensity scoring showed that the eGCX in the db/db group was significantly thinner than that in the db/+ group. These results were consistent with the scanning electron microscopy findings. In contrast, treatment with nafamostat mesylate significantly improved the flap engraftment rate and suppressed eGCX injury. In conclusion, treatment with nafamostat mesylate improves the disrupted eGCX structure of skin flap tissue in db/db mice, potentially ameliorating the impaired capillary-to-venous return in the skin flap tissue.

Potential Indicators of Intestinal Necrosis in Portal Venous Gas: A Case Report of an 82-Year-Old Woman on Long-Term Hemodialysis with Ascites and Pneumatosis Coli.

BACKGROUND Several factors have been reported as possible predictors of intestinal necrosis in patients with portal venous gas (PVG). We describe potential indicators of intestinal necrosis in PVG identified by contrasting 3 episodes of PVG in a patient on hemodialysis against previously verified factors. CASE REPORT An 82-year-old woman undergoing hemodialysis was admitted to our hospital thrice for acute abdominal pain. On first admission, she was alert, with a body temperature of 36.3°C, blood pressure (BP) of 125/53 mmHg, pulse rate of 60/min, respiratory rate of 18/min, and 100% oxygen saturation on room air. Computed tomography (CT) revealed PVG, intestinal distension, poor bowel wall enhancement, bubble-like pneumatosis in the intestinal wall, and minimal ascites. PVG caused by intestinal ischemia was diagnosed, and she recovered after bowel rest and hydration. Three months later, she had a second episode of abdominal pain. BP was 115/56 mmHg. CT revealed PVG and a slight accumulation of ascites, without pneumatosis in the intestinal wall. She again recovered after conservative measures. Ten months later, the patient experienced a third episode of abdominal pain, with BP of 107/52 mmHg. CT imaging indicated PVG, considerable ascites, and linear pneumatosis of the intestinal walls. Despite receiving conservative treatment, the patient died. CONCLUSIONS A large accumulation of ascites and linear pneumatosis in the intestinal walls could be potential indicators of intestinal necrosis in patients with PVG caused by intestinal ischemia. As previously reported, hypotension was further confirmed to be a reliable predictor of intestinal necrosis.