Management of COVID-19 Infection in a Small Bowel Transplant Recipient: A Case Report.

The COVID-19 pandemic has caused millions of people to become infected worldwide. Some patients may have disease progression and may need treatment with an anti-COVID-19 agent, hospitalization, and even intensive care. The risk factors for disease progression include old age, diabetes mellitus, pulmonary disease, cardiac disease, immunodeficiency, and immunosuppressant treatment. Therefore, managing COVID-19 infection in transplant patients under immunosuppressant treatments needs specific consideration, especially the side effects of anti-COVID-19 agents and the interaction between immunosuppressants and anti-COVID-19 agents. In this report, we present the case of a small bowel transplant patient who had a COVID-19 infection. The patient was initially treated for paxlovid, and she developed bloody stools and dizziness. The treatment was then changed to molnupiravir without discontinuation of tacrolimus. The patient recovered smoothly after a 5-day treatment with molnupiravir. Here, we discuss the management experience of such patients and review the relevant literature.

Efficacy of same venous route Hickman catheter replacement in patients with intestinal failure.

BACKGROUND/PURPOSE: Periodical replacement of venous Hickman catheters is required for the nutritional care of patients with intestinal failure. The conventional de novo operation (DN-OP) involves inserting the catheter into a new venous tract in each replacement; however, this could result in fast consumption of functional central vessels in patients with intestinal failure. Recently, same-route operation (SR-OP) has been adopted as an alternative approach for retaining venous access. METHODS: We conducted a retrospective study to compare the efficacy of Hickman catheters and the survival of venous vessels using two different operative strategies. RESULTS: Overall, 181 catheters were inserted, 109 using DN-OP and 72 using SR-OP. The mean catheter duration was 11.9 ± 8.8 months in the DN-OP group and 10.5 ± 5.6 months in the SR-OP group; the infection rate was 0.74 in the DN-OP group and 0.44 in the SR-OP group. The vein accesses used in these insertions (n = 113) were classified: the DN-vein group for veins accessed only by DN-OP (n = 75) and the SR-vein group for veins accessed by an initial DN-OP and subsequent SR-OPs (n = 38). Mean working duration per vein access was 12.3 ± 10.1 months in the DN-vein group and 28.2 ± 14.8 months in the SR-vein group (p < 0.001); mean infection-free duration was 11.4 ± 10.1 months in the DN-vein group and 27.7 ± 15.3 months in the SR-vein group (p < 0.001). CONCLUSION: Application of SR-OP in Hickman catheter replacement significantly extended the working duration of venous access by re-using the same venous route without compromising catheter efficacy in patients with IF having poor venous access.

The impact of the COVID-19 outbreak on activation of the massive transfusion protocol in the emergency department.

BACKGROUND AND OBJECTIVES: An outbreak of coronavirus disease 2019 (COVID-19) occurred in mid-May of 2021 in Taiwan. After 2 months of hard work, transmissions were successfully prevented and the number of newly confirmed COVID-19 cases fell remarkably. We evaluated the impact of this outbreak on the massive transfusion protocol (MTP) in the emergency department (ED) of a trauma centre. MATERIALS AND METHODS: We retrospectively compared the activation and efficacy of MTP before, during and after the outbreak by analysing the clinical data relevant to MTP activations. RESULTS: There was no remarkable change in the average number of MTP triggers per month during the outbreak. The interval from an MTP trigger to the first unit of blood transfused at bedside was significantly increased during the outbreak compared to that before the outbreak (22.4 min vs. 13.9 min, p < 0.001); while the 24-h survival rate decreased (57.1% vs. 71.1%, p = 0.938). There were no remarkable changes in blood unit return or wastage during the outbreak. CONCLUSION: The COVID-19 outbreak limitedly affected MTP activation and waste of blood products, but significantly increased the interval from an MTP trigger to the first unit of blood transfused at bedside.

The predictive and prognostic role of hematologic and biochemical parameters in the emergency department among coronavirus disease 2019 patients.

Coronavirus disease 2019 (COVID-19) had caused a worldwide pandemic with public health emergencies since 2020. For the symptomatic patients, high mortality rate was observed if without timely and optimized management. In this study, we aimed to investigate the predictive and prognostic roles of hematologic and biochemical parameters obtained in the emergency department (ED) for COVID-19 patients. We conducted a retrospective study in a dedicated COVID-19 medical center, recruiting a total of 228 COVID-19 patients with 86 severe and 142 non-severe cases. Both the hematologic and biochemical parameters obtained in the ED upon arrival were analyzed to evaluate the association of the biomarkers with disease severity and prognosis among COVID-19 patients. Among these parameters, neutrophil-to-lymphocyte ratio (NLR), C-reactive protein (CRP), procalcitonin (PCT), lactate dehydrogenase (LDH), ferritin, and D-dimer were significantly higher in the severe group than the non-severe one, whereas the platelet count and lymphocyte-to-monocyte ratio were significantly lower. Receiver operating characteristic curve analysis revealed that the areas under curve of CRP, PCT, LDH, ferritin, D-dimer, and NLR for differentiating the severity of COVID-19 were 0.713, 0.755, 0.763, 0.741, 0.733, and 0.683, respectively, whereas the areas under curve of CRP, PCT, LDH, ferritin, D-dimer, and NLR for differentiating the mortality of COVID-19 were 0.678, 0.744, 0.680, 0.676, 0.755, and 0.572, respectively. Logistic regression analysis revealed that CRP, PCT, LDH, ferritin, D-dimer, and NLR were independent indicators for prediction of severe COVID-19, and LDH and ferritin were independent factors associated with the mortality in COVID-19. In conclusion, higher CRP, PCT, LDH, ferritin, D-dimer, and NLR were associated with severe COVID-19, whereas higher LDH and ferritin were associated with the mortality in COVID-19. These findings could help early risk stratification in the ED and contribute to optimized patient management.

VS-5584, a PI3K/mTOR dual inhibitor, exerts antitumor effects on neuroblastomas in vitro and in vivo.

BACKGROUND: The phosphatidylinositol-3-kinase (PI3K)/protein kinase B (AKT)/mammalian target of rapamycin (mTOR) pathway is closely related to oncogenesis. PI3K/mTOR inhibitors are considered capable of counteracting the feedback mechanisms within the pathway. In this study, we investigated the antitumor effects of VS-5584, an orally administered PI3K/mTOR dual inhibitor, on neuroblastomas. METHODS: The effects of VS-5584 on proliferation, cell cycle distribution, and related signaling molecules were examined in neuroblastoma cells using the (3-[4,5-dimethylthiazole-2-yl]-2,5-diphenyltetrazolium bromide)-based colorimetric assay, flow cytometry, and western blotting, respectively. Nude mice were subcutaneously inoculated with human neuroblastoma cells, followed by VS-5584 treatment for two weeks. Tumor growth was tracked and tumor tissues were subjected to immunohistochemical investigations. RESULTS: In neuroblastoma cells, VS-5584 significantly inhibited proliferation and induced G0/G1 cell cycle arrest. Additionally, VS-5584 decreased the expression of phospho-S6 kinase 1 (p-S6K1), p-retinoblastoma protein, p-cyclin-dependent kinase 2, and cyclin E1, and increased the expression of p21 and p27 in neuroblastoma cells. In mice, VS-5584 significantly suppressed tumor growth in neuroblastomas and downregulated the expression of p-mTOR and p-S6K1 in tumor tissues. CONCLUSIONS: VS-5584 blocks the PI3K/mTOR pathway, induces a G0/G1 cell cycle arrest, and exerts antitumor effects on neuroblastomas both in vitro and in vivo.

Surveillance of Rejection After Intestinal Transplantation Using an Image Enhanced Endoscopy "VENCH" Scoring System.

BACKGROUND: Graft rejection after intestinal transplantation remains challenging. We aimed to use endoscopy for rejection prediction. MATERIALS AND METHODS: Patients ≥7 years old who underwent intestinal transplantation between November 2016 and September 2019 were prospectively enrolled. Magnifying endoscopy under narrow-band imaging was performed through ileostomy. Endoscopic findings were reported as five components (each graded from 0-2): "V" (villi appearance), "E" (erythema), "N" (capillary network), "C" (crypt widening), and "H" (heterogeneity). The correlation between histological severity and endoscopic score was analyzed. RESULTS: Ninety-nine endoscopic biopsies from three female and one male patient were analyzed. The mean ± SD age was of 41.25±13.77 (range 29-58) years. Three short bowel syndrome patients after multiple intestinal resections and one with chronic intestinal pseudo-obstruction were indicated for intestinal transplantation. Sensitivity, specificity, and accuracy of V, E, N, C, and H scores for predicting rejection were 97.4%, 45.9%, 65.7%; 94.7%, 70.5%, 79.8%; 97.4%, 52.5%, 69.7%; 94.7%, 54.1%, 69.7%; and 97.4%, 62.3%, 75.8%, respectively. Pearson's correlation coefficients between total and individual V, E, N, C, H scores and histological rejection were 0.79, 0.64, 0.70, 0.71, 0.73, and 0.66, respectively (P < .001). To predict mild and moderate/severe rejection, total scores more than 4 and 6 had the sensitivity/specificity of 87.50%/57.38% and 96.67%/85.25%, respectively (area under the ROC 0.791 and 0.987). CONCLUSION: Endoscopic VENCH scoring is promising for predicting rejection after IT. More studies are warranted to validate such results. (ClinicalTrials.gov number, NCT03616548.).

AZD8055 Exerts Antitumor Effects on Colon Cancer Cells by Inhibiting mTOR and Cell-cycle Progression.

BACKGROUND/AIM: AZD8055 is an inhibitor of mammalian target of rapamycin (mTOR) that can suppress both mTOR complex 1 (mTORC1) and mTORC2. This study investigated the antitumor effects of AZD8055 on colon cancer. MATERIALS AND METHODS: The effects of AZD8055 on proliferation, apoptosis, and cell cycle of colon cancer cells, and tumor growth in a mouse colon cancer model were studied. RESULTS: AZD8055 significantly inhibited proliferation and induced apoptosis of colon cancer cells (p<0.05). The phosphorylation of both AKT and S6 kinase 1 (S6K1) was suppressed by AZD8055. AZD8055 also induced G0/G1 cell-cycle arrest, reduced cyclin D1 and increased p27 expression, and suppressed the levels of phospho-cyclin-dependent kinase 2 and phospho-retinoblastoma. Compared to the control, oral administration of AZD8055 significantly suppressed tumor growth in mice (p<0.05). CONCLUSION: AZD8055 induces cytotoxicity, apoptosis, and cell-cycle arrest of colon cancer cells, and exerts an antitumor effect in mice. It also inhibits the mTOR signaling pathway and mTOR-dependent cell-cycle progression.

Proactive Consultation by a Clinical Pathologist Prevents Diagnostic Delay in Hematological Malignancies.

BACKGROUND: Diagnostic difficulties in hematological malignancies may lead to unacceptably prolonged help-seeking to diagnostic interval as well as increased complications and poor outcomes. Proactive consultation by a clinical pathologist (PCCP) may help clinical diagnosis and therapeutic strategy. Hence, the aim of this investigation was to evaluate the effect of PCCP on the help-seeking to diagnostic interval in hematological cancer cases. MATERIALS AND METHODS: From January to November, 2015, abnormal results of hematological laboratory testing with added laboratory comment were selectively screened out, and patients with such abnormalities in hematological laboratory testing and accompanied laboratory comment with PCCP were enrolled. RESULTS: A total of 125 aberrant results of hematological laboratory testing were given with accompanied laboratory comments with PCCP and 40.8% (n=51) of these patient-oriented comments had an effect on clinical diagnosis and therapeutic strategy. Twelve of the subjects belonged to newly diagnosed hematological malignancies with the assistance of PCCP, and the help-seeking to diagnostic interval was also shortened from 42 days to 26 days in chronic lymphoid leukemia (CLL), from 83 days to 11 days in multiple myeloma (MM), and from 128 days to 15 days in myelodysplastic syndrome/myeloproliferative neoplasm (MDS/MPN). During the monitoring interval, neither complication events nor deaths were reported in the study group. CONCLUSIONS: It was seemingly that PCCP prevented diagnostic delay in hematological malignancies via shortening the help-seeking to diagnostic interval, particularly in CLL, MM and MDS/MPN cases. PCCP can be considered to play an essential role in prompt establishment of diagnosis in hematological malignancies for those who newly present.

Clinical Practice of Blood Transfusion in Orthotopic Organ Transplantation: A Single Institution Experience.

BACKGROUND: Orthotopic organ transplantation, a treatment option for irreversible organ dysfunction according to organ failure, severe damaged organ or malignancy in situ, was usually accompanied with massive blood loss thus transfusion was required. We aimed to evaluate the adverse impact of blood transfusion on solid organ transplantation. MATERIALS AND METHODS: From January, 2009 to December, 2014, patients who received orthotopic organ transplantation at Far Eastern Memorial Hospital medical center were enrolled. Clinical data regarding anemia status and red blood cell (RBC) transfusion before, during and after operation, as well as patient outcomes were collected for further univariate analysis. RESULTS: A total of 105 patients who underwent orthotopic transplantation, including liver, kidney and small intestine were registered. The mean hemoglobin (Hb) level upon admission and before operation were 11.6 ± 1.8 g/dL and 11.7 ± 1.7 g/dL, respectively; and the nadir Hb level post operation and the final Hb level before discharge were 8.3 ± 1.6 g/dL and 10.2 ± 1.6 g/dL, respectively. The median units (interquartile range) of RBC transfusion in pre-operative, peri-operative and post-operative periods were 0 (0-0), 2 (0-12), and 2 (0-6) units, respectively. Furthermore, the median (interquartile range) length of hospital stay (LHS) from admission to discharge and from operation to discharge were 28 (17-44) and 24 (16-37) days, respectively. Both peri-operative and post-operative RBC transfusion were associated with longer LHS from admission to discharge and from operation to discharge. Furthermore, it increased the risk of post-operative septicemia. While peri-operative RBC transfusion elevated the risk of acute graft rejection in patients who received orthotopic transplantation. CONCLUSIONS: Worse outcome could be anticipated in those who had received massive RBC transfusion in transplantation operation. Hence, peri-operative RBC transfusion should be avoided as much as possible.

Creatine Kinase (CK)-MB-to-Total-CK Ratio: a Laboratory Indicator for Primary Cancer Screening.

BACKGROUND: For the determination of creatine kinase (CK)-MB, the immunoinhibition method is utilized most commonly. However, the estimated CK-MB activity may be influenced by the presence of CK isoenzymes in some conditions like cancer. Thus, a CK-MB-to-total-CK ratio more than 1.0 could be found in such a situation. The study aimed to explore the relationship of cancer to high CK-MB-to-total-CK ratio. MATERIALS AND METHODS: From January 2011 to December 2014, laboratory data on all CK-MB and total CK test requests were extracted at Far Eastern Memorial Hospital (88,415 requests). Patients with a CK-MB-to-total-CK ratio more than 1.0 were registered in this study. Clinical data including tumor location, tumor TNM stage and metastatic status were also collected. RESULTS: A total of 846 patients were identified with a CK-MB-to-total-CK ratio more than 1.0. Of these, 339 (40.1%) were diagnosed with malignancies. The mean CK-MB-to-total-CK ratio was significantly higher in malignancy than in non-malignancy (1.35±0.28 vs 1.25±0.23, p<0.001) groups. The most frequent malignancy with a CK-MB-to-total-CK ratio more than 1.0 was colorectal cancer (1.42±0.28, 16.5%, n=56), followed by lung cancer (1.38±0.24, 15.9%, n=54) and hepatocellular carcinoma (14.5%, n=49). Higher CK-MB-to-total-CK ratios in hematological malignancies (1.44±0.41)were also noted. Additionally, the CK-MB-to-total-CK ratio was markedly higher in advanced stage malignancy than in early stage (1.37±0.26 vs. 1.29±0.31, p=0.014) and significantly higher in liver metastasis than in non-liver metastasis (1.48±0.30 vs. 1.30±0.21, p<0.001). CONCLUSIONS: The CK-MB-to-total-CK ratio is an easily available indicator and could be clinically utilized as a primary screening tool for cancer. Higher ratio of CK-MB-to-total-CK was specifically associated with certain malignancies, like colorectal cancer, lung cancer and hepatocellular carcinoma, as well as some cancer-associated status factors such as advanced stage and liver metastasis.

Tumors Involving Skin, Soft Tissue and Skeletal Muscle: Benign, Primary Malignant or Metastatic?

BACKGROUND: Metastatic cancer with invasion of skin, soft tissue and skeletal muscle is not common. Examples presenting as soft tissue masses could sometimes lead to misdiagnosis with delayed or inappropriate management. The purpose of current study was to investigate clinical characteristics in the involvement of metastatic cancer. MATERIALS AND METHODS: A total of 1,097 patients complaining of skin or soft tissue masses and/or lesions were retrospectively reviewed from January 2012 to June 2013. Tumors involving skin, soft tissue and skeletal muscle of head and neck, chest wall, abdominal wall, pelvic region, back, upper and lower extremities were included in the study. RESULTS: Fifty-seven (5.2%) patients were recognized as having malignancies on histopathological examination. The most common involvement of malignancy was basal cell carcinoma, followed by cutaneous squamous cell carcinoma, sarcoma and melanoma. The most common anatomical location in skin and soft tissue malignancies was head and neck (52.6% of the malignancies). Four (0.36%) of the malignant group were identified as metastatic cancer with the primary cancer source from lung, liver and tonsil and the most common site was upper extremities. One of them unexpectedly expired during the operation of metastatic tumor excision at the scalp. CONCLUSIONS: Discrimination between benign and malignant soft tissue tumors is crucial. Performance of imaging study could assist in the differential diagnosis and the pre-operative risk evaluation of metastatic tumors involving skin, soft tissue and skeletal muscle.

Diagnostic Role of Serum Free-to-Total Prostate Specific Antigen (PSA) Ratio in Prostate Cancer with Serum Total Concentration of PSA below 4 ng/mL.

PURPOSE: To examine the effectiveness of serum free-to-total prostate specific antigen ratio (%fPSA) for the detection of prostate cancer (PCa) in men with different serum total PSA (tPSA) categories. MATERIALS AND METHODS: From January 2010 to December 2013, a total of 225 patients with lower urinary tract symptoms (LUTS) underwent tPSA and %fPSA measurements. Histological examination with calculation of Gleason score and whole body bone scans were performed in identified cases of PCa. RESULTS: PCa was diagnosed in 44 (19.6%) patients and the remaining 181 patients had benign prostate disease. PCa was detected in 5 (23.8%), 13 (8.7%) and 26 (47.3%) cases with tPSA level ranges≤4 ng/ml, 4 to 10 ng/ml and >10 ng/ml, respectively. The average Gleason score was 7.2±0.2. Some 6 (13.6%) out of 44 PCa patients had bone metastases. The sensitivity was 80% and specificity was 81.3% at the cut-off %fPSA of 15% in PCa patients with a tPSA level below 4 ng/ mL. A lower %fPSA was associated with PCa patients with Gleason score≥7 than those with Gleason score≤6 (11.7±0.98 vs. 16.5±2.25%, P=0.029). No obvious relation of %fPSA to the incidence of bone metastasis was apparent in this study. CONCLUSIONS: The clinical application of %fPSA could help to discriminate PCa from benign prostate disease in men with a tPSA concentration below 4 ng/mL.

Clinical features of patients with esophageal and second primary cancers.

BACKGROUND: The prevalence of esophageal cancer (EC) with second primary cancers (SPC) is increasing worldwide. This study was aimed to understand the clinical features of EC patients with SPC in the Taiwanese population. MATERIALS AND METHODS: Clinical and laboratory data for 180 EC patients with or without SPC were collected between January 2009 and December 2013. Information on treatment approaches, location of SPCs and ABO blood type were also collected and stratified. RESULTS: The most common SPC in EC patients was hypopharyngeal cancer, followed by laryngeal cancer and hepatocellular carcinoma in our study. Malignancies of colon, prostate and lung were also found. There was a significant higher portion of blood type A in the EC patients with SPC compared with those without (42.4% vs 19.5%, P=0.006). CONCLUSIONS: The frequency and SPC site distribution and blood type A should be considered in clinical evaluation of EC patients with a high risk of developing SPC in the Taiwanese population.