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BackgroundTo determine the clinical importance of pneumatosis intestinalis (PI) on surgical decision-making and patient outcomes.MethodsA matched cohort observational study was conducted including all clinical encounters for both ambulatory and inpatient care at UCLA Health between February 15, 2006 and January 31, 2023. Patients were initially identified using encounter diagnostic codes for "other specified diseases of intestine." A radiologic diagnosis of PI was then assessed using natural language processing techniques followed by confirmation using manual chart review. Patients who did not have PI served as a control group. Patient comorbidity was assessed using Elixhauser comorbidity scores. Logistic regression and Cox hazard analyses were used to assess associations between PI and mortality. The main outcome was 90-day all-cause mortality. Secondary outcomes were the proportion of patients undergoing surgery and, of those, how many required bowel resections.ResultsOf the 16,728 patients identified by diagnostic coding, 315 were confirmed to have a diagnosis of PI. The 90-day mortality rate for all patients with PI was 29%. Surgery was performed for 62 patients (20%), of whom 46 (72%) underwent bowel resection and 16 (28%) underwent abdominal exploration alone. Most patients underwent surgery for peritonitis (37%), bowel obstruction (31%), and/or pneumoperitoneum (23%) in association with PI; whereas only 8% of patients received surgery exclusively for PI. There was no statistically significant association between PI and mortality with logistic regression conditioned on other risk factors for mortality. In contrast, survival analysis of a matched cohort demonstrated a small effect of PI on mortality (hazard ratio = 1.24: 95% confidence interval = 1.16-1.32, P = 0.021).ConclusionsMost patients with a diagnosis of PI survive without requiring surgery. Of those who undergo surgery, nearly all have indications for laparotomy exclusive of PI. Mortality in patients who have pneumatosis is strongly associated with comorbid disease, with little to no independent association with PI. Our findings suggest that the presence of PI should not be a primary indication for surgical intervention.

BackgroundmTORC1 activity is dependent on the presence of micronutrients, including Asparagine (Asn), to promote anabolic cell signaling in many cancers. We hypothesized that targeting Asn metabolism would inhibit tumor growth by reducing mTORC1 activity in well-differentiated (WD)/dedifferentiated (DD) liposarcoma (LPS).MethodsHuman tumor metabolomic analysis was utilized to compare abundance of Asn in WD vs. DD LPS. Gene set enrichment analysis (GSEA) compared relative expression among metabolic pathways upregulated in DD vs. WD LPS. Proliferation assays were performed for LPS cell lines and organoid models by using the combination treatment of electron transport chain (ETC) inhibitors with Asn-free media. 13C-Glucose-labeling metabolomics evaluated the effects of combination treatment on nucleotide synthesis. Murine xenograft models were used to assess the effects of ETC inhibition combined with PEGylated L-Asparaginase (PEG-Asnase) on tumor growth and mTORC1 signaling.ResultsAsn was enriched in DD LPS compared to WD LPS. GSEA indicated that mTORC1 signaling was upregulated in DD LPS. Within available LPS cell lines and organoid models, the combination of ETC inhibition with Asn-free media resulted in reduced cell proliferation. Combination treatment inhibited nucleotide synthesis and promoted cell cycle arrest. In vivo, the combination of ETC inhibition with PEG-Asnase restricted tumor growth.ConclusionsAsn enrichment and mTORC1 upregulation are important factors contributing to WD/DD LPS tumor progression. Effective targeting strategies require limiting access to extracellular Asn and inhibition of de novo synthesis mechanisms. The combination of PEG-Asnase with ETC inhibition is an effective therapy to restrict tumor growth in WD/DD LPS.

BackgroundSmall bowel obstruction (SBO) is common and its management has evolved in recent years.Study designThe literature describing adhesive small bowel obstruction (aSBO) treatment was reviewed, and a formal systematic review was performed to identify publications reporting results of aSBO treatment without NGTs.ResultsThe annual rate of hospital admission for SBO in the US has increased, with 340,100 admissions in 2019 alone. SBO is usually treated with bowel rest, intravenous hydration and NGT placement. In recent years, water soluble contrast (WSC) has been used as a cathartic to simulate bowel function and may reduce hospital length of stay (HLOS) by 1.95 days (95%CI 0.56-3.3). There were 3 articles of the initial 1650 screened that reported outcomes of SBO treatment without NGTs. These articles included 759 patients, of whom 272 (36%) with aSBO were managed successfully without NGTs. When comparing outcomes to patients who did receive NGT decompression, there were no significant differences in operative rates (28.6% v 16.5%, risk ratio 1.34, 95% CI 1.0, 1.8). Mortality and rates of bowel resection were also not affected by NGT decompression (risk ratio 1.98, 95% CI 0.43, 9.10 and risk ratio 1.56, 95% CI 0.92, 2.65, respectively).ConclusionSBO is a common disease process with increasing annual incidence. Use of WSC stimulates the bowel and may reduce HLOS. Modern aSBO treatment protocols should include NGT decompression with consideration of WSC administration. Selection of patients for treatment without NGT decompression requires further investigation.

BackgroundAlthough IGF2BP3 has been implicated in tumorigenesis and poor outcomes in multiple cancers, its role in soft-tissue sarcoma (STS) remains unknown. Preliminary data have suggested an association with IGF2BP3 expression among patients with well-differentiated/dedifferentiated liposarcoma (WD/DD LPS), a disease where molecular risk stratification is lacking.MethodsWe examined the survival associations of IGF2BP3 via univariate and multivariate Cox regression in three unique datasets: (1) the Cancer Genome Atlas (TCGA), (2) an in-house gene microarray, and (3) an in-house tissue microarray (TMA). A fourth dataset, representing an independent in-house TMA, was used for validation.ResultsWithin the TCGA dataset, IGF2BP3 expression was a poor prognostic factor uniquely in DD LPS (OS 1.6 vs. 5.0 years, p = 0.009). Within the microarray dataset, IGF2BP3 expression in WD/DD LPS was associated with worse survival (OS 7.7 vs. 21.5 years, p = 0.02). IGF2BP3 protein expression also portended worse survival in WD/DD LPS (OS 3.7 vs. 13.8 years, p < 0.001), which was confirmed in our validation cohort (OS 2.7 vs. 14.9 years, p < 0.001). In the multivariate model, IGF2BP3 was an independent risk factor for OS, (HR 2.55, p = 0.034).ConclusionIGF2BP3 is highly expressed in a subset of WD/DD LPS. Across independent datasets, IGF2BP3 is also a biomarker of disease progression and worse survival.

Background: Various population-based studies have shown Hispanic/Latino ethnicity is a risk factor for worse survival in patients with gastric cancer linked to disparate access to care. We aimed to address whether Hispanic patients treated within safety-net hospital systems continue to experience this survival deficit compared to non-Hispanic patients. Methods: We performed a retrospective cohort study comparing survival between Hispanic and non-Hispanic patients diagnosed with gastric adenocarcinoma between January 1, 2016, and December 31, 2020, within Los Angeles County's safety-net hospital system. Gastric cancer-specific survival was compared between the two cohorts using the Kaplan-Meier estimate and Cox proportional-hazards regression model. Results: In total, 448 patients who received care from five medical centers were included; 348 (77.7%) patients self-identified as Hispanic and 100 (22.3%) as non-Hispanic. Mean follow-up time was 2.0 years (median 0.91 years, IQR, 0.34-2.5 years). Hispanic patients were found to be diagnosed at a younger age (55.6 vs. 60.7 years, P < 0.01), demonstrate higher state area deprivation index (6.4 vs. 5.0, P < 0.01), and present with metastatic disease (59.8% vs. 45%, P = 0.04). After adjusting social and oncologic variables, Hispanic ethnicity remained an independent risk factor for worse survival [HR 1.56, (95% CI, 1.06-2.28); P = 0.02]. Conclusions: Hispanic patients treated within a large, multicenter safety-net hospital system experience worse survival compared to non-Hispanic patients. This suggests ethnic disparities exist within safety-net hospital systems, independent of known clinicopathologic factors. Impact: Improving outcomes for Hispanic patients with gastric cancer requires future efforts aimed at defining and addressing these unidentified barriers to care. [ABSTRACT FROM AUTHOR]

Carcinosarcomas are rare malignant tumors derived of both epithelial and mesenchymal elements. Herein, we report an elderly man originally diagnosed with a squamous cell carcinoma of the hand. Upon excision, the tumor was found to be a more aggressive carcinosarcoma. Immunohistochemical stains revealed that the sarcoma component of the lesion was vimentin positive, whereas the primary carcinoma tumor cells were positive for p63 and CK903. Both components were negative for CD34 and D2-40. This tumor was found to have angiolymphatic invasion and eventually metastasized to the axillary lymph nodes and lungs.

Hemorrhagic transformation is a severe complication of acute ischemic stroke owing to its limited treatment options and poor prognosis. In the last decade, the rates of hemorrhagic transformation incidence have been associated with blood glucose levels. In particular, hyperglycemia at the time of admission has been associated with increased rates of hemorrhagic transformation in acute ischemic stroke patients. Recent pilot clinical trials have attempted to use intensive insulin therapy during stroke treatment to reduce the severity of cerebral infarction and possibly alleviate the risk of hemorrhagic transformation. However, the results of these studies have shown no clear clinical benefit. In addition, intensive insulin therapy has increased rates of hypoglycemia which may be associated with larger infarct growth. We hypothesize that hypoglycemia, similarly to hyperglycemia, is a risk factor for worse outcomes in acute ischemic stroke by promoting hemorrhagic transformation. This review serves to call attention to patterns present within intensive insulin therapy trials and shed light into the pathophysiological effects of hypoglycemia. It is critical that efforts be directed toward the prevention of hemorrhagic transformation by optimizing insulin therapy during the treatment of acute ischemic stroke. [ABSTRACT FROM AUTHOR]

Aims: Exposure to recurrent hypoglycemia (RH) is common in diabetic patients receiving glucose‐lowering therapies and is implicated in causing cognitive impairments. Despite the significant effect of RH on hippocampal function, the underlying mechanisms are currently unknown. Our goal was to determine the effect of RH exposure on hippocampal metabolism in treated streptozotocin‐diabetic rats. Methods: Hyperglycemia was corrected by insulin pellet implantation. Insulin‐treated diabetic (ITD) rats were exposed to mild/moderate RH once a day for 5 consecutive days. Results: The effect of RH on hippocampal metabolism revealed 65 significantly altered metabolites in the RH group compared with controls. Several significant differences in metabolite levels belonging to major pathways (eg, Krebs cycle, gluconeogenesis, and amino acid metabolism) were discovered in RH‐exposed ITD rats when compared to a control group. Key glycolytic enzymes including hexokinase, phosphofructokinase, and pyruvate kinase were affected by RH exposure. Conclusion: Our results demonstrate that the exposure to RH leads to metabolomics alterations in the hippocampus of insulin‐treated streptozotocin‐diabetic rats. Understanding how RH affects hippocampal metabolism may help attenuate the adverse effects of RH on hippocampal functions. [ABSTRACT FROM AUTHOR]

The objective of this systematic review was to investigate the etiologies of hair loss of the eyebrow and eyelash that required hair transplantation, the optimal surgical technique, patient outcomes, and common complications. A total of 67 articles including 354 patients from 18 countries were included in this study. Most patients were women with an average age of 29 years. The most common etiology requiring hair transplantation was burns, occurring in 57.6 percent of cases. Both eyebrow and eyelash transplantation use follicular unit transplantation techniques most commonly; however, other techniques involving composite grafts and skin flaps continue to be utilized effectively with minimal complication rates. In summary, many techniques have been developed for use in eyebrow/eyelash transplantation and the selection of technique depends upon the dermatologic surgeon's preferences and the unique presentations of their patients. [ABSTRACT FROM AUTHOR]

Background: Gastric cancer disproportionately impacts populations in resource-limited settings. Within a safety-net network, we assessed the utility of computed tomography (CT) as a single staging modality., Methods: We utilized a clinical database of gastric cancer patients treated within the Los Angeles County safety-net hospital system from 2016 to 2023 in conjunction with retrospective imaging review by certified radiologists. We assessed agreement between clinical and pathological staging for patients who underwent curative gastrectomy using the Kappa coefficient., Results: Of 107 patients with available CT imaging, 43.9% (n = 47) were staged with CT as a single modality. Most tumors displayed infiltrating (75%) or diffuse (28%) morphology, 41% displayed adequate gastric distention and regional lymphadenopathy was common (68%). Twenty-nine patients underwent curative gastrectomy. Overall agreement was minimal (κ = 0.29, 95% CI [0.071-0.51], p = 0.022), weak for T3/T4 tumors (κ = 0.50, 95% CI [0.17-0.82], p < 0.01), and weak for Hispanic/Latino patients (κ = 0.47, 95% CI [0.19-0.76], p < 0.01)., Conclusions: There was minimal agreement between clinical and pathologic staging when assessing clinical stage by CT imaging alone, suggesting that CT is not adequate as a single modality staging tool. While every effort should be made to obtain multimodal staging, larger studies are warranted to improve CT imaging protocols for staging in resource-limited settings., (© 2024 The Author(s). Journal of Surgical Oncology published by Wiley Periodicals LLC.)

A 64-year-old man was referred to our dermatology clinic with a diagnosis of Muir-Torre syndrome (MTS), he had a history of multiple sebaceous carcinomas and sebaceous adenomas removed over the years. The patient has also had visceral cancer and had undergone a colon resection 17 years before to treat colon cancer and was recently diagnosed with invasive high-grade urothelial carcinoma of the right ureter. In addition, the patient has an extensive family history of cancer; a pedigree was constructed to document this history (Figure 1). Of note is that the patient's mother and father were second cousins. The patient's father was diagnosed with lung cancer at age 57 and died of colon cancer at the age of 72. The patient's mother died of colon cancer at age 74. The patient has three siblings: a sister and two brothers. The sister died of bone cancer at age 42. One brother had a number of cancers including colon, kidney, and skin cancers and died at age 53. His other brother is alive and has a history of colon cancer, kidney cancer, and ureteral cancer. The patient has five children. He has a 40-year-old son who, at the age of 30, was diagnosed with testicular cancer. His daughters are 47, 44, 39, and 34, with no history of malignancy to date. The patient had three maternal aunts, all of whom succumbed to colon cancer, as well as two paternal uncles who died of lung cancer. The patient's maternal grandfather was a smoker and he also died of lung cancer.

Eruptive xanthomatosis is described as the sudden eruption of erythematous yellow papules in the presence of hypertriglyceridemia, often associated with serum triglyceride levels above 2000 mg/dl. Severe hypertriglyceridemia can be caused by primary genetic mutations, secondary chronic diseases, or a combination of both. Uncontrolled diabetes mellitus is a known risk factor. It is imperative for physicians to be aware of eruptive xanthomatosis as a warning sign for severe hypertriglyceridemia due to the underlying risk for the potentially fatal complication of acute pancreatitis. Herein, we discuss a case of a 52-year-old man with uncontrolled diabetes mellitus who presented with eruptive xanthomata and a triglyceride level of 7157 mg/dl, the highest recorded value in the absence of acute pancreatitis, with a remarkable response to drug therapy. A review of the literature is included to discuss the clinical relevance and appropriate treatment of this disease entity., Competing Interests: There are no conflicts of interest.