Correction: Huang et al. Systemic Anticoagulation and Inpatient Outcomes of Pancreatic Cancer: Real-World Evidence from U.S. Nationwide Inpatient Sample. Cancers 2023, 15, 1985.

In the original publication [...].

Effects of SGLT2 inhibitors on clinical cancer survival in patients with type 2 diabetes.

PURPOSE: According to the preclinical data, sodium-glucose cotransporter 2 (SGLT2) inhibitors (SGLT2is) may exert anticancer effects. Here, we clarified the cancer-specific mortality (primary outcome) and all-cause mortality (secondary outcome) of SGLT2is and their dose-dependency in patients with cancer undergoing standard curative treatments. METHODS: We analyzed data from patients with type 2 diabetes mellitus (T2DM) diagnosed with cancer between January 1, 2016, and December 31, 2018, enrolled from the Taiwan Cancer Registry database. Kaplan-Meier method was used to estimate all-cause mortality and cancer-specific mortality, comparing survival curves between SGLT2i users and nonusers using the stratified log-rank test. Cox proportional hazards regression was conducted to identify independent predictors for all-cause and cancer-specific mortality among the covariates. RESULTS: We performed 1:2 propensity score matching of our data, which yielded a final cohort of 50,133 patients with cancer; of them, 16,711 and 33,422 were in the SGLT2i user and nonuser groups, respectively. The adjusted hazard ratio (aHR) for cancer-specific and all-cause mortality in SGLT2i users compared with nonusers was 0.21 (95 % confidence interval [CI]: 0.20-0.22) and 0.22 (95 % CI: 0.21-0.23). We divided the patients into four subgroups stratified by quartiles (Q) of cumulative defined daily doses per year (cDDDs), and all-cause and cancer-specific mortality was noted to significantly decrease with increases in dosage (from Q1 to Q4 cDDDs) in SGLT2i users compared with in nonusers (P < 0.001). CONCLUSION: SGLT2is increase overall survival and cancer-specific survival in patients with cancer in a dose-dependent manner.

Efficacy, safety and cost of emicizumab prophylaxis in haemophilia A patients with inhibitors: A nationwide observational study in Taiwan.

INTRODUCTION: Emicizumab mimicking the cofactor function of activated factor VIII (FVIII) restores haemostasis. METHODS: This nationwide observational study aimed to retrospectively investigate efficacy, safety, and cost in 1 year before and up to 3 years after emicizumab prophylaxis for haemophilia A (HA) patients with FVIII inhibitors. RESULTS AND DISCUSSION: A total of 39 severe HA patients with a median age of 23.0 years were enrolled. The median historical peak FVIII inhibitor titre was 174.2 BU/mL with an interquartile range of 56.5-578.8 BU/mL. The median annualized bleeding rate reduced from 24 to 0 events in the first year after emicizumab prophylaxis (p < .01) and sustained in the second and third years. The median annualized joint bleeding rate reduced to 0 and maintained up to 3 years (p < .01). Twenty-seven patients (69.2%) had target joints before emicizumab prophylaxis and only seven patients (17.9%) of them had target joints after prophylaxis. Medical costs, including cost of haemostatic therapy, frequency of outpatient department visits, emergency room visits and hospital admission, were significantly reduced after emicizumab prophylaxis (p < .01). FVIII inhibitor titre decreased after emicizumab prophylaxis. Overall, three (7.7%) patients experienced 202 grade 1 drug-related adverse events after emicizumab prophylaxis. No serious adverse events were reported during emicizumab prophylaxis period. The adherence to emicizumab prophylaxis was 100% up to 3 years. CONCLUSIONS: HA patients with FVIII inhibitors treated with emicizumab prophylaxis resulted in a significant reduction in treated bleeds and associated costs. No new safety events were observed.

Systemic Anticoagulation and Inpatient Outcomes of Pancreatic Cancer: Real-World Evidence from U.S. Nationwide Inpatient Sample.

Background: Pancreatic cancer can induce a hypercoagulable state which may lead to clinically apparent thrombosis. However, the effect of anticoagulants remains ambiguous. This study aimed to investigate the potential effect of long-term systemic anticoagulant usage on hospitalization outcomes of patients with pancreatic cancer. Methods: This retrospective study extracted all data from the U.S. Nationwide Inpatient Sample (NIS) database from 2005 to 2018. We included hospitalized adults ≥18 years old with a pancreatic cancer diagnosis identified by International Classification of Diseases ninth revision (ICD-9) and tenth revision (ICD-10) codes. We utilized diagnostic codes ICD9 V58.61 and ICD10 Z79.01, i.e., 'long-term use of anticoagulant', to identify individuals who were on a long-term systemic anticoagulant. The study cohort were then further grouped as being with or without long-term systemic use of an anticoagulant. Propensity score matching was performed to balance the characteristics of the two groups. The risks of life-threatening events, e.g., acute myocardial infarction (AMI), acute heart failure (AHF), sepsis, shock, and acute kidney injury (AKI), in-hospital death, and prolonged length of stay (LOS) in the hospital were compared between the groups by univariable and multivariable logistic regression analyses. Results: The study population consisted of 242,903 hospitalized patients with pancreas cancer, 6.5% (n = 15,719) of whom were on long-term systemic anticoagulants. A multivariable regression analysis showed that long-term systemic anticoagulant use was independently associated with lower odds of sepsis (aOR: 0.81, 95% CI: 0.76-0.85), shock (aOR: 0.59, 95% CI: 0.51-0.68), AKI (aOR: 0.86, 95% CI: 0.81-0.91), in-hospital mortality (aOR: 0.65, 95% CI: 0.60-0.70), and prolonged LOS (aOR: 0.84, 95% CI: 0.80-0.89). Conclusions: Long-term systemic anticoagulant use is associated with better clinical outcomes in terms of decreased risks of some life-threatening events, in-hospital death, and prolonged LOS among hospitalized patients with pancreatic cancer in the U.S.

Prediction of survival time after terminal extubation: the balance between critical care unit utilization and hospice medicine in the COVID-19 pandemic era.

BACKGROUND: We established 1-h and 1-day survival models after terminal extubation to optimize ventilator use and achieve a balance between critical care for COVID-19 and hospice medicine. METHODS: Data were obtained from patients with end-of-life status at terminal extubation from 2015 to 2020. The associations between APACHE II scores and parameters with survival time were analyzed. Parameters with a p-value ≤ 0.2 in univariate analysis were included in multivariate models. Cox proportional hazards regression analysis was used for the multivariate analysis of survival time at 1 h and 1 day. RESULTS: Of the 140 enrolled patients, 76 (54.3%) died within 1 h and 35 (25%) survived beyond 24 h. No spontaneous breathing trial (SBT) within the past 24 h, minute ventilation (MV) ≥ 12 L/min, and APACHE II score ≥ 25 were associated with shorter survival in the 1 h regression model. Lower MV, SpO2 ≥ 96% and SBT were related to longer survival in the 1-day model. Hospice medications did not influence survival time. CONCLUSION: An APACHE II score of ≥ 25 at 1 h and SpO2 ≥ 96% at 1 day were strong predictors of disposition of patients to intensivists. These factors can help to objectively tailor pathways for post-extubation transition and rapidly allocate intensive care unit resources without sacrificing the quality of palliative care in the era of COVID-19. Trial registration They study was retrospectively registered. IRB No.: 202101929B0.

Safety and effectiveness of transdermal buprenorphine in cancer pain: An observational study in Taiwan (SOOTHE).

AIM: Buprenorphine is one of the strongest opioids used for the relief of cancer pain. This study aims to evaluate the real-world clinical experiences of transdermal buprenorphine used in moderate to severe cancer pain in the Asian population. METHODS: This is an open-labeled, multicenter, 4-week observational study. Stable cancer pain patients who decided to switch the previous opioid to transdermal buprenorphine will be enrolled in this study. The safety and effectiveness were observed and collected. Pain assessment was performed using a numerical rating scale by the investigators and the Brief Pain Inventory Short Form (BPI-SF) by the patient. The safety profiles included concomitant medications and adverse events (AEs). RESULTS: A total of 83 patients were enrolled in this study. The global pain scores in the BPI, as well as the four individual pain parameters (worst, least, average, and right now), showed a continued decrease (p < .05) from week 2 to week 4. Significant improvements were observed in normal work activities, relations with other people, sleep, enjoyment of life, and global BPI pain interference score on week 4. Pain assessments conducted by investigators demonstrated significant, continuous improvements during the study periods. In addition, transdermal buprenorphine demonstrated good safety/tolerability with limited drug-related AEs in the Asian population with cancer pain. CONCLUSION: This study demonstrated that transdermal buprenorphine in the Asian population has good safety profiles and continued improvements in pain relief, sleep, and pain interferences. Transdermal buprenorphine can be an effective and convenient option as a transdermal opioid for patients with moderate to severe cancer pain in Taiwan. (NCT Number: NCT04315831).

Transdermal buprenorphine improves overall quality of life and symptom severity in cancer patients with pain.

AIM AND OBJECTIVES: This study explored the effect of transdermal buprenorphine on quality of life and six symptoms in cancer patients with pain. BACKGROUND: Transdermal opioids offer advantages over traditional routes of administration. The impact of transdermal buprenorphine on quality of life for patients with cancer in Asian populations is unknown. DESIGN: This study employed a single-arm observational repeated measures design. Cancer patients with pain were evaluated prior to treatment (baseline). Over a 4-week treatment period, quality of life and symptoms were assessed at 2 and 4 weeks. This study adhered to the recommendations of STROBE guidelines. METHODS: This multi-site study was conducted in six hospitals located across northern, middle and southern Taiwan. Adult cancer patients whose pain was previously stable with opioid analgesics and, based on clinical judgement, were able to convert to transdermal buprenorphine treatment were invited to participate. Quality of life was measured with the European Organization for Research and Treatment of Cancer (EORTC) Quality of Life Questionnaire Core 30 (QLQ-C30). RESULTS: Generalised estimating equations showed participants who completed at least one follow-up measurement (N = 80) over 4-weeks had a significant improvement in overall quality of life. Functional status only improved for social functioning. However, symptom severity decreased significantly for nausea/vomiting, pain, insomnia and constipation. CONCLUSIONS: The study provides initial evidence supporting transdermal buprenorphine for providing beneficial effects of improving quality of life and reducing severity of symptoms in Asian patients with cancer. RELEVANCE TO CLINICAL PRACTICE: The findings of this study can inform the clinical practice that the use of transdermal buprenorphine in cancer patients with pain may also reduce the severity of other symptoms and improve overall quality of life. TRIAL REGISTRATION DETAILS: This study was registered in ClinicalTrials.gov. Identifier: NCT04315831.

Effect of sleep disorders on the risks of cancers and site-specific cancers.

PURPOSE: Whether preexisting sleep disorder is an independent risk factor for cancer remains unclear. Therefore, we performed this propensity score-matched population-based cohort study to compare the incidence rate ratios (IRRs) of specific cancers between patients with and without sleep disorders. PATIENTS AND METHODS: Patients were categorized into two groups on the basis of the presence or absence of sleep disorders and matched at a 1:1 ratio. RESULTS: Propensity score matching yielded a final cohort of 289,162 patients (i.e., 144,581 and 144,581 in the sleep disorder and nonsleep disorder groups, respectively) who were eligible for further analysis. In multivariate Cox regression analysis, the adjusted hazard ratio (aHR; 95% confidence interval [CI]) of cancer risk in the sleep disorder group compared with the nonsleep disorder group was 1.07 (1.04-1.12; P = 0.0001). Furthermore, the adjusted IRRs (95% CIs) for all cancers, breast cancer, and ovarian cancer in the patients with sleep disorders were 1.08 (1.02-1.18), 1.20 (1.08-1.32), and 1.30 (1.10-1.52), respectively. CONCLUSION: The results suggested that sleep disorders are a significant risk factor for all cancers, breast cancer, and ovarian cancer.

Sarcopenia Is an Independent Risk Factor for Severe Diabetic Nephropathy in Type 2 Diabetes: A Long-Term Follow-Up Propensity Score-Matched Diabetes Cohort Study.

Background: Diabetic nephropathy is a common cause of chronic kidney disease (CKD) and end-stage kidney disease (ESKD) worldwide and results in tremendous wastage of medical resources. Determining the indicators of diabetic nephropathy, such as sarcopenia, and implementing early interventions to prevent disease progression is crucial. Purpose: The effect of sarcopenia on the risk of severe diabetic nephropathy in patients with type 2 diabetes (T2DM) remains unclear. Patients and Methods: We recruited patients with T2DM and categorized them into two groups, propensity score−matched at a ratio of 1:1, according to whether they had sarcopenia. We subsequently compared the groups' risk of severe diabetic nephropathy. Results: The matching process yielded a final cohort of 105,166 patients with T2DM (52,583 and 52,583 in the sarcopenia and nonsarcopenia groups, respectively) who were eligible for inclusion in subsequent analyses. According to both the univariate and multivariate Cox regression analyses, the adjusted hazard ratio (aHR) (95% confidence interval) of severe diabetic nephropathy for the sarcopenia diabetes group compared with the control group was 1.10 (1.08−1.13; p < 0.001). Conclusion: The patients with T2DM and sarcopenia were at a higher risk of severe diabetic nephropathy than were those without sarcopenia. Our results may serve as a valuable reference for relevant government authorities in establishing health policies to promote early detection of sarcopenia and exercise to help patients with T2DM overcome sarcopenia.

Primary intracranial malignant melanomas in solitary type: a tertiary center experience.

PURPOSE: Solitary type primary intracranial malignant melanoma (PIMM) is extremely rare but fatal. The optimal treatment algorithm according to clinical relevance of symptoms and outcomes is unclear. This series emphasized the prognostic factors of solitary PIMM and established the treatment algorithm for this rare disease. METHODS: Patients with solitary PIMMs were pathologically verified and treated with neurosurgical tumor resection. All solitary PIMMs recruited at our institute received multidisciplinary team care. We analyzed the clinical findings and prognostic factors. RESULTS: The study cohort included 10 patients. PIMMs in solitary type impacted middle-aged populations with male predominance in Taiwan. Most patients (80%) presented a single tumor initially. Six patients had progressed to multiplicity after the initial treatment. Rates of tumor bleeding and leptomeningeal metastasis seeding (LS) are high in solitary PIMMs. Patients who had gross-total resection (GTR) had better survival than those who had incomplete resection, with median overall survival (OS) rates of 170.4 months vs. 5.23 months (p = 0.004). Multiplicity, eloquent area involvement, initial tumor bleeding, LS, hydrocephalus, and Karnofsky Performance Score < 80 at diagnosis were associated with negative outcomes in progression-free survival and OS. Adjuvant radiotherapy for patients who had LS and for those who cannot undergo grossly total tumor removal resulted in a good outcome. CONCLUSIONS: GTR demonstrated better outcomes for solitary PIMM. For recurrent tumors, aggressively repeated surgical resection remained beneficial for selected cases. Adjuvant radiotherapy was a treatment option for LS following operation. We proposed a possible treatment algorithm for solitary PIMM.

Case Report: Vaccine-Induced Immune Thrombotic Thrombocytopenia in a Pancreatic Cancer Patient After Vaccination With Messenger RNA-1273.

Vaccination plays an important role during the COVID-19 pandemic. Vaccine-induced thrombotic thrombocytopenia (VITT) is a major adverse effect that could be lethal. For cancer patients, cancer-related thromboembolism is another lethal complication. When cancer patients receive their COVID-19 vaccines, the following thromboembolic events will be more complicated. We presented a case recently diagnosed with pancreatic cancer, who had received the mRNA-1273 (Moderna) vaccination 12 days prior. Ischemic stroke and VITT were also diagnosed. We aggressively treated the patient with steroids, immunoglobulin, and plasma exchange. The titer of anti-platelet factor four and d-dimer level decreased, but the patient ultimately died. The complicated condition of VITT superimposed cancer-related thromboembolism was considered. To our knowledge, only one case of mRNA-1273 related VITT was reported, and this case study was the first to report a cancer patient who was diagnosed with VITT after mRNA-1273 vaccination. Therefore, when the need for vaccination among cancer patients increased under the current COVID-19 pandemic, the possible risk of VITT for cancer patients should be carefully managed. Further studies of the risk evaluation of the COVID-19 vaccine in cancer patients might be required in the future.

Distinct immunoglobulin heavy chain variable region gene repertoire and lower frequency of del(11q) in Taiwanese patients with chronic lymphocytic leukaemia.

Chronic lymphocytic leukaemia (CLL) is the most common leukaemia in Western countries but very rare in Asia. Peripheral blood or bone marrow mononuclear cells obtained at initial diagnosis from 194 patients with CLL were analysed to determine the ethnic difference in genetic abnormalities. Mutated IGHV was detected in 71·2% of Taiwanese CLL and IGHV3-23 was the most frequently used gene. Stereotyped BCR was present in 18·3% with subset 8 being the most frequent. All cases with subset 8 belonged to IGHV 4-39 and were exclusively associated with un-mutated IGHV and poor outcome. Mutation frequencies of SF3B1 (9·7%), NOTCH1 (8·6%), BIRC3 (1·1%), ATM (16·9%) or TP53 (8·1%), and frequencies of cytogenetic abnormalities including trisomy 12 (18·6%), del(17p) (10·4%), del(13q) (43·7%) and IGH translocation (10·1%) were comparable to those reported from Western countries, except del(11q) (6·9%) which was lower in our patients. Patients with un-mutated IGHV, subset 8, disrupted TP53, trisomy 12, and SF3B1 mutations had a worse outcome compared to patients without these mutations. In conclusion, IGHV3-23 usage, stereotyped subset 8 and lower frequency of del(11q) show an ethnicity-dependent association in Taiwanese CLL patients.

Prognostic nutritional index relevance in chemoradiotherapy for advanced oral cavity, oropharyngeal and hypopharyngeal cancer.

BACKGROUND AND OBJECTIVES: This study was designed to evaluate the impact of the prognostic nutritional index (PNI) on treatment-related toxicities and tolerance in patients with advanced head and neck cancers who were undergoing concurrent chemoradiotherapy (CCRT). METHODS AND STUDY DESIGN: We retrospectively analyzed and compared the clinical characteristic, toxicities and survival of 143 patients with stage III, IVA, and IVB head and neck cancer who were treated with CCRT according to their PNI between 2007 and 2010. RESULTS: Low PNI was correlated with T classification and advanced tumor stage. Patients with low PNI were less likely to tolerate CCRT, required tube feeding support more frequently and had higher percentages of grade 3/4 hematological toxicities, sepsis and toxic death. CONCLUSIONS: Pretreatment PNI predicts treatment-tolerance and toxicity in patients with advanced head and neck cancer undergoing CCRT.

Cognitive Machine-Learning Algorithm for Cardiac Imaging: A Pilot Study for Differentiating Constrictive Pericarditis From Restrictive Cardiomyopathy.

BACKGROUND: Associating a patient's profile with the memories of prototypical patients built through previous repeat clinical experience is a key process in clinical judgment. We hypothesized that a similar process using a cognitive computing tool would be well suited for learning and recalling multidimensional attributes of speckle tracking echocardiography data sets derived from patients with known constrictive pericarditis and restrictive cardiomyopathy. METHODS AND RESULTS: Clinical and echocardiographic data of 50 patients with constrictive pericarditis and 44 with restrictive cardiomyopathy were used for developing an associative memory classifier-based machine-learning algorithm. The speckle tracking echocardiography data were normalized in reference to 47 controls with no structural heart disease, and the diagnostic area under the receiver operating characteristic curve of the associative memory classifier was evaluated for differentiating constrictive pericarditis from restrictive cardiomyopathy. Using only speckle tracking echocardiography variables, associative memory classifier achieved a diagnostic area under the curve of 89.2%, which improved to 96.2% with addition of 4 echocardiographic variables. In comparison, the area under the curve of early diastolic mitral annular velocity and left ventricular longitudinal strain were 82.1% and 63.7%, respectively. Furthermore, the associative memory classifier demonstrated greater accuracy and shorter learning curves than other machine-learning approaches, with accuracy asymptotically approaching 90% after a training fraction of 0.3 and remaining flat at higher training fractions. CONCLUSIONS: This study demonstrates feasibility of a cognitive machine-learning approach for learning and recalling patterns observed during echocardiographic evaluations. Incorporation of machine-learning algorithms in cardiac imaging may aid standardized assessments and support the quality of interpretations, particularly for novice readers with limited experience.

Dasatinib-related chylothorax.

Dasatinib is a potent second-generation tyrosine kinase inhibitor for the treatment of chronic myeloid leukemia. The most common adverse event associated with dasatinib therapy is fluid retention, including pleural effusion. Dasatinib-related chylothorax has rarely been reported. The clinical manifestations, pathophysiology, management, and prognosis are not fully understood. Here we report a 40-year-old woman presenting with chylothorax following dasatinib use. We propose the hypothesis of its mechanism as well as offering a review of the relevant literature.

Chronic lymphocytic leukemia presenting with ascites diagnosed by clonality analysis via gene rearrangement assay: A case report.

The diagnosis of chronic lymphocytic leukemia (CLL) presenting with ascites is predominantly based on the morphological and immunophenotypic characteristics, which are comparable to peripheral blood and bone marrow cells. However, it is relatively difficult to diagnose CLL due to the pleomorphism of the lymphocytes in ascites. The current study presents an 80-year-old male with a prior diagnosis of CLL who developed large ascites. Predominant T lymphocytes rendered morphological and immunophenotypic diagnosis difficult. Clonality analysis of immunoglobulin (Ig) gene rearrangements was performed on the lymphocytes from the ascites to diagnose the involvement of CLL, a laparotomy and biopsy from the peritoneal node confirmed the involvement of small lymphocytic lymphoma/CLL. The clonality analysis of Ig gene rearrangements may provide a powerful and accurate method for diagnosing CLL presenting with ascites.

Gastric and colonic metastases from primary lung adenocarcinoma: A case report and review of the literature.

Lung cancer is one of the leading causes of cancer-related mortality worldwide. Gastrointestinal metastasis from primary lung cancer is rare. Only a few reports have been published and the majority of described metastatic sites involved the small intestine. In the present study, we report the first case of primary lung adenocarcinoma with both gastric and colonic metastases. We also review the published literature of primary lung cancer with gastrointestinal metastasis.