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At least 1,495 records · Page 83Linked to original sources
PubMed1997

Urokinase plasminogen activator receptor (uPA-R): one potential characteristic of metastatic phenotypes in minimal residual tumor disease.

Evidence of dynamic development of cytokeratin (CK) 18-positive disseminated tumor cells in bone marrow of curatively resected cancer patients has implicated a subclinical minimal residual disease as a biologically relevant component in solid cancer. However, differentiation between irrelevant shed cells and those cells potentially capable of causing later recurrence has not yet been made. In parallel, accumulating data show functional association of the urokinase plasminogen activator (uPA) system and the membranous uPA receptor (uPA-R) with the capacity of a tumor cell for invasion and metastasis. The present study was designed to find descriptive evidence in vivo concerning whether uPA-R could be one potential characteristic for metastatically relevant phenotypes of disseminated tumor cells. An immunocytochemical double staining for uPA-R and CK18 (immunogold/alkaline phosphatase anti-alkaline phosphatase) was performed on perioperative and follow-up bone marrow aspirations of 78 curatively resected gastric cancer patients, if positive tumor cell status had been shown previously with the single alkaline phosphatase anti-alkaline phosphatase method. Bone marrow cells (10(6)) were examined in each assay. Postoperative qualitative and quantitative development of uPA-R-expressing disseminated tumor cells was followed in relation to uPA-R-negative cells and correlated with later clinical relapse. Double staining could be performed perioperatively or in follow-up, or both, in 58 of 78 patients. Expression of uPA-R on perioperatively disseminated tumor cells significantly correlated with later quantitative increases of tumor cells (P = 0.0009). Overall median tumor cell numbers with uPA-R expression significantly increased during follow-up from a median value of 5.5 to 10.0 in 10(6) cells (P = 0.008), and the mean relative percentage of uPA-R-positive, compared with uPA-R-negative, disseminated tumor cells also increased, from 47.9% at surgery to 68.6% in follow-up (P < 0.001). This was mainly due to patients with later tumor relapse (increase from 63.9 to 80.7%, P = 0.001). Patients without relapse showed slight increases at lower percentage levels (5.7% at surgery, 7.4% in follow-up). Differences for relapsing patients were significant (surgery, P = 0.006; follow-up, P < 0.001). Our results suggest from an in vivo model that uPA-R may be one antigen that enables identification and follow-up observations of metastatically relevant phenotypes of disseminated tumor cells, differentiating their individual potential for causing relapse.

Adult↗
PubMed2004

Incorporation of functional imaging data in the evaluation of dose distributions using the generalized concept of equivalent uniform dose.

Advances in the fields of IMRT and functional imaging have greatly increased the prospect of escalating the dose to highly active or hypoxic tumour sub-volumes and steering the dose away from highly functional critical structure regions. However, current clinical treatment planning and evaluation tools assume homogeneous activity/function status in the tumour/critical structures. A method was developed to incorporate tumour/critical structure heterogeneous functionality in the generalized concept of equivalent uniform dose (EUD). The tumour and critical structures functional EUD (FEUD) values were calculated from the dose-function histogram (DFH), which relates dose to the fraction of total function value at that dose. The DFH incorporates flouro-deoxyglucose positron emission tomography (FDG-PET) functional data for tumour, which describes the distribution of metabolically active tumour clonogens, and single photon emission computed tomography (SPECT) perfusion data for critical structures. To demonstrate the utility of the method, the lung dose distributions of two non-small cell lung cancer patients, who received 3D conformal external beam radiotherapy treatment with curative intent, were evaluated. Differences between the calculated lungs EUD and FEUD values of up to 50% were observed in the 3D conformal plans. In addition, a non-small cell lung cancer patient was inversely planned with a target dose prescription of 76 Gy. Two IMRT plans (plan-A and plan-B) were generated for the patient based on the CT, FDG-PET and SPECT treatment planning images using dose-volume objective functions. The IMRT plans were generated with the goal of achieving more critical structures sparing in plan-B than plan-A. Results show the target volume EUD in plan-B is lower than plan-A by 5% with a value of 73.31 Gy, and the FEUD in plan-B is lower than plan-A by 2.6% with a value of 75.77 Gy. The FEUD plan-B values for heart and lungs were lower than plan-A by 22% and 18%, respectively. While EUD values show plan-A is marginally better than plan-B in terms of target volumetric coverage, the FEUD plan-B values show adequate target function coverage with significant critical structure function sparing. In conclusion, incorporating functional data in the calculation of EUD is important in evaluating the biological merit of treatment plans.

Carcinoma, Non-Small-Cell Lung↗
PubMed2004

Reirradiation of recurrent head and neck cancers with curative intent.

In patients with recurrent, previously irradiated head and neck cancer, the traditional therapy of palliative single- or multi-agent chemotherapy yields a 30% to 40% response rate with median survival durations of 8 to 10 months. However, long-term survival is rarely observed. Reirradiation with or without concurrent chemotherapy is currently under investigation as a treatment option in these patients. While reirradiation without chemotherapy appears to be effective in recurrent nasopharynx cancer cases, the use of concomitant chemotherapy with reirradiation appears to offer improved outcomes based on phase I/II data in other head and neck sites. Recent studies indicate that long-term survival of patients is possible following reirradiation in a minority of cases despite severe acute and chronic toxicities. Reirradiation with chemotherapy is appropriate for patients with a goal of long-term local control of disease and curative intent, despite the risk of significant acute and late toxicities.

Combined Modality Therapy↗
PubMed1987

Forecast of surgical risk in pancreatic cancer.

Over a 22 year period, 305 patients underwent operations for pancreatic cancer. Seventy-one patients who only underwent a laparotomy and 60 patients with defective data were excluded from our study. The remaining 174 patients were analyzed to find a clinically applicable algorithm to allow the preoperative surgical risk to be evaluated in a single patient. One hundred twenty-six had undergone a bypass operation (Group I) and 48, a potentially curative resection (Group II). The two groups were divided into the following three risk groups according to the postoperative course: D, patients who died during the first postoperative month; C, patients with postoperative complications; and U, patients with an uneventful course. Preoperative weight loss, duration of jaundice, serum bilirubin level, total protein level, and age of every patient were collected and transformed into a three-score ordinal scale. Stepwise discriminant analysis of these data enabled us to correctly classify 88 percent of the patients who underwent palliative operations and 83 percent of those who had pancreatic resection. This method is useful in identifying the risk group for a single patient using individual preoperative variables. It may, moreover, suggest the most suitable treatment for each patient with pancreatic cancer.

Adult↗
PubMed2005

Investigation of protein functions through data-mining on integrated human transcriptome database, H-Invitational database (H-InvDB).

H-Invitational Database (H-InvDB; ) is a human transcriptome database, containing integrative annotation of 41,118 full-length cDNA clones originated from 21,037 loci. H-InvDB is a product of the H-Invitational project, an international collaboration to systematically and functionally validate human genes by analysis of a unique set of high quality full-length cDNA clones using automatic annotation and human curation under unified criteria. Here, 19,574 proteins encoded by these cDNAs were classified into 11,709 function-known and 7865 function-unknown hypothetical proteins by similarity with protein databases and motif prediction (InterProScan). The proportion of "hypothetical proteins" in H-InvDB was as high as 40.4%. In this study, we thus conducted data-mining in H-InvDB with the aim of assigning advanced functional annotations to those hypothetical proteins. First, by data-mining in the H-InvDB version of GTOP, we identified 337 SCOP domains within 7865 H-Inv hypothetical proteins. Second, by data-mining of predicted subcellular localization by SOSUI and TMHMM in H-InvDB, we found 1032 transmembrane proteins within H-Inv hypothetical proteins. These results clearly demonstrate that structural prediction is effective for functional annotation of proteins with unknown functions. All the data in H-InvDB are shown in two main views, the cDNA view and the Locus view, and five auxiliary databases with web-based viewers; DiseaseInfo Viewer, H-ANGEL, Clustering Viewer, G-integra and TOPO Viewer; the data also are provided as flat files and XML files. The data consists of descriptions of their gene structures, novel alternative splicing isoforms, functional RNAs, functional domains, subcellular localizations, metabolic pathways, predictions of protein 3D structure, mapping of SNPs and microsatellite repeat motifs in relation with orphan diseases, gene expression profiling, and comparisons with mouse full-length cDNAs in the context of molecular evolution. This unique integrative platform for conducting in silico data-mining represents a substantial contribution to resources required for the exploration of human biology and pathology.

Amino Acid Sequence↗
PubMed2005

Claudin-10 expression level is associated with recurrence of primary hepatocellular carcinoma.

PURPOSE: Hepatocellular carcinoma (HCC) patients with the same clinicopathologic features can have remarkably different disease outcomes after curative hepatectomy. To address this issue, we evaluated the cDNA microarray gene expression profiles of HCCs and identified claudin-10 expression level was associated with disease recurrence. The aim of the current study is to validate the microarray data by an alternative research method applicable for routine practice. EXPERIMENTAL DESIGN: Quantitative reverse transcription-PCR (RT-PCR) was used to validate the microarray data on claudin-10 expression level. The assay was repeated on a separate HCC sample set to consolidate the prognostic significance of claudin-10. RESULTS: Claudin-10 expression level by quantitative RT-PCR and by microarray measurement showed a high concordance (r = 0.602, P < 0.001). Quantitative RT-PCR was repeated on a separate HCC sample set and the association of claudin-10 expression with recurrence was again confirmed (hazard ratio, 1.2; 95% confidence interval, 1.0-1.4; P = 0.011). By multivariable Cox regression analysis, claudin-10 expression and pathologic tumor-node-metastasis stage were independent factors for prediction of disease recurrence. CONCLUSION: Claudin-10 expression of HCC can be used as a molecular marker for disease recurrence after curative hepatectomy.

Carcinoma, Hepatocellular↗
PubMed1991

Calculation of half-life of carcinoembryonic antigen after lung tumour resection: a case report.

Since little is known about carcinoembryonic antigen (CEA) half-life in humans, we followed changes in CEA levels after curative resection of a small bronchial adenocarcinoma in a 54 yr old man with an unusually high preoperative serum CEA level of 1,199 ng.ml-1. Serum CEA followed a four phase curve with an initial increase, attributed to release of CEA from the tumour, a rapid fall during four days (CEA half-life 3.2 days), a slower exponential decay to normal levels during almost three months (CEA half-life 11 days) and eventually maintenance of normal levels for 14 months. These results are consistent with data from animal experiments and a single report on CEA half-life in humans, but CEA half-life seems longer in man than in animals. This observation also suggests that a very high serum CEA level should not in itself preclude curative surgical resection of a primary bronchogenic carcinoma.

Adenocarcinoma, Bronchiolo-Alveolar↗
PubMed1993

Early detection of occult colorectal hepatic metastases using duplex colour Doppler sonography.

Previous studies have shown that overt intrahepatic tumours are associated with subtle changes in liver perfusion that can be measured directly using duplex colour Doppler sonography (DCDS). This study assessed the predictive value of DCDS in the early detection of occult colorectal hepatic metastases. Hepatic arterial and portal venous blood flow was measured in 50 control subjects and 135 patients with colorectal cancer, 67 with overt liver metastases and 68 with an apparently disease-free liver on the basis of computed tomography and laparotomy findings. The Doppler perfusion index (DPI), defined as the ratio of hepatic arterial to total liver blood flow, was calculated. Clear separation of the DPI values of controls and those of patients with overt metastases was observed (P < 0.0001). Thirty-eight of the 68 patients with a disease-free liver also had an abnormally high DPI value. After 1 year of follow-up, 21 patients with an abnormally high DPI at the time of apparently curative primary resection had developed liver metastases and a further four had died without post-mortem examination. The 30 patients with normal DPI remain disease-free. The data suggest that DPI is of value in the early detection of occult liver metastases.

Adult↗
PubMed2006

Tumor length as a prognostic factor in esophageal malignancy: univariate and multivariate survival analyses.

BACKGROUND AND OBJECTIVES: Gastrointestinal specialists generally feel that long esophageal tumors carry a worse prognosis and are likely to be more advanced than shorter lesions. Our aim was to investigate the relationship between histologically determined tumor length and aspects of tumor pathology and survival for patients with resected esophageal malignancy. METHODS: Three hundred and nine patients who underwent esophageal resection with curative intent in our unit between 1994 and 2003 were retrospectively analyzed. Pathological details such as TNM stage, differentiation, completeness of surgical resection, and overall stage were collected. Survival data were obtained for each patient and univariate and multivariate analyses were performed. Overall survival was used as the primary endpoint. RESULTS: There were 225 adenocarcinomas, 72 squamous cell carcinomas, and 12 other tumor types with a median tumor length of 3.5 cm (range 0.5-14 cm). Tumor length greater than 3.5 cm was associated with increasing T stage (P = 0.0001), N stage (P = 0.032), overall stage (P = 0.003), and involvement of the longitudinal resection margins (P = 0.02). Univariate analysis found tumor length greater than 3.5 cm was associated with worse overall survival compared with shorter tumors (P = 0.0002). Tumor length remained a significant prognostic factor on multivariate analysis (P = 0.04). Other prognostic factors on multivariate analysis were age, tumor differentiation, nodal involvement, and resection margin status. CONCLUSION: Tumor length greater than 3.5 cm (as determined histologically) is associated with worse disease stage and poor overall patient survival. If preoperative endoscopic tumor length bears a similar relationship, this could assist in patient selection for appropriate treatments.

Adenocarcinoma↗
PubMed1997

Targets for gene therapy of Parkinson's disease: growth factors, signal transduction, and promoters.

Parkinson's disease gene therapy is in its infancy. All studies to date have been in experimental animals and there are no clinical protocols currently approved. Several non-human primate studies however, have been completed and preliminary data appear promising. When dealing with a complex acquired disorder of unknown etiology, gene therapy is likely to provide symptomatic and palliative relief at best and will not be curative. However, if the gene therapy approach has advantages in terms of the risk/benefit ratio, cost and efficacy over current treatments, then it should be brought to clinical trial. This article discusses some future directions and areas of intense investigation at present. The advances in the field over the past five years have been tremendous and it appears possible that before the year 2000, clinical gene therapy trials in Parkinson's disease will be ongoing.

Animals↗
PubMed2004

Can early diagnosis of symptomatic colorectal cancer improve the prognosis?

Patients with colorectal cancer continue to present with relatively advanced tumors. Delay in diagnosis is often believed to have been a contributing factor, and the validity of this hypothesis has seldom been questioned. The aim of this study was to establish whether a delay in diagnosis is related to long-term survival and if the most frequent symptoms were related to the stage or time at which the carcinoma was diagnosed. Data from 660 patients surgically treated for uncomplicated colorectal carcinoma in our institution between 1985 and 2000 were analyzed retrospectively. Age, sex, initial symptoms, duration of symptoms, neoplasm location, curative surgery, TNM stage, and survival time were the variables recorded. Patients were classified into two groups according to symptom duration: < 3 months versus >/= 3 months. Comparative statistical analysis was performed for the two groups as well as the initial symptom, TNM stage, and survival time. Also, the initial symptoms most frequently reported were compared with the TNM stage. The two groups were found to be equal with regard to distribution of age, gender, location of the neoplasm, type of surgery performed, and TNM stage. We found that symptom duration was shortened in the presence of abdominal pain ( p = 0.002) [odds ratio (OR) 0.53; 95% confidence interval (CI) 0.35-0.80] and was delayed in the presence of an anemic syndrome ( p = 0.006) (OR 2.4; 95% CI 1.27-4.56). Also, the stage of the neoplasm was related to rectal bleeding ( p < 0.001) and abdominal pain ( p = 0.008). The log-rank test indicated that duration of symptoms was not related to long-term survival ( p = 0.90). We concluded that the duration of colorectal cancer symptoms is not related to the stage or prognosis of tumors.

Adult↗
PubMed2006

What is the link between nonlocalizing sestamibi scans, multigland disease, and persistent hypercalcemia? A study of 401 consecutive patients undergoing parathyroidectomy.

BACKGROUND: We hypothesized that nonlocalizing sestamibi scans would correlate with multigland disease and persistent primary hyperparathyroidism. METHODS: We reviewed records for 401 consecutive patients who underwent parathyroidectomy from 1999 to 2004. Gender, age, preoperative imaging, surgical findings, gland weight and volume, and 6-month calcium levels (Ca) were examined. RESULTS: We identified 289 women and 112 men, 297 of whom had a preoperative sestamibi scan localized to a single gland (localized group; LG). Ninety-six percent of the LG were found to have single-gland disease, and 4% had multigland disease (MGD). In the nonlocalized group (NLG), 76% had single-gland disease and 24% MGD. Mean gland weight was greater in the LG than in the NLG (1128 mg vs 699 mg; P < .05). Mean gland volume was larger in the LG (1.34 cc vs 0.89 cc; P < .05). A localizing sestamibi scan had a positive predictive value (PPV) of 96% and a likelihood ratio of 2.29 for predicting "curative" intraoperative parathyroid hormone drop after removal of a single abnormal gland. Patients were stratified into normocalcemic (NCa) and hypercalcemic (HCa) groups based on 6-month postoperative serum calcium data (n = 328). HCa incidence at 6 months did not differ significantly between the LG (5%) and NLG (3%). A localizing scan had a PPV of 95% for normocalcemia at 6 months. A nonlocalizing scan had a PPV of 21% for HCa at 6 months. CONCLUSIONS: Nonlocalizing sestamibi scans were more common in primary hyperparathyroidism with MGD and were associated with smaller-volume abnormal glands found at operation. Preoperative sestamibi scan-results did not predict HCa at 6 months.

Adenoma↗
PubMed2000

Pretreatment plasma TGF beta 1 levels are prognostic for survival but not morbidity following radiation therapy of carcinoma of the cervix.

PURPOSE: To determine whether pretreatment plasma-transforming growth factor beta 1 (TGF beta 1) levels are prognostic for tumor control and late morbidity following radiation therapy in carcinoma of the cervix. METHODS AND MATERIALS: The study was comprised of 79 patients undergoing radiotherapy with curative intent for Stage I-III carcinoma of the cervix. TGF beta 1 levels were analyzed using ELISA. Late morbidity was measured using the Franco-Italian glossary. Data were available for the pretreatment levels of circulating tumor markers that represent disease burden, and for peripheral blood lymphocyte radiosensitivity measured as SF2. RESULTS: Pretreatment TGF beta 1 levels were a significant prognostic factor for survival and local control. There were weak significant correlations of TGF beta 1 levels with disease stage and the levels of circulating tumor markers (CA125, TPA). There was a weak significant correlation between TGF beta 1 levels and normal cell radiosensitivity (lymphocyte SF2). There was no relationship between TGF beta 1 levels and grade of morbidity and pretreatment TGF beta 1 levels were not a significant prognostic factor for the probability of developing late morbidity. CONCLUSION: In carcinoma of the cervix, pretreatment TGF beta 1 levels reflect tumor burden and are a significant prognostic factor for survival. Despite an underlying weak relationship of TGF beta 1 levels with intrinsic normal cell radiosensitivity, pretreatment levels are not prognostic for the probability of developing late complications. This finding does not rule out the possible usefulness of measurements toward the end of treatment once tumor burden has been reduced.

Adenocarcinoma↗
PubMed2000

Mucosectomy for gastric cancer: current status in Japan.

Advances in techniques of image diagnosis have enabled the detection of minute or small cancer lesions in the stomach. Patients with such cancer, in principle, were treated surgically, but accumulated histopathological data on surgical cancer specimens revealed that many of these patients did not have any metastatic lesions. For those localized cancers, local treatment of primary lesions by endoscopy gives curative results. It has been demonstrated that endoscopic therapy is curative in mucosal well-differentiated adenocarcinoma not more than 20 mm in diameter without ulceration. Efforts to cure early gastric cancer without surgery yielded fruitful results and a new treatment concept was established. Even if there is a recurrence of the residual or metachronous lesions, they can be treated by further endoscopic treatment.

Endoscopy↗
PubMed2002

Prognostic significance of intratumoural microvessel density (IMD) in resected pancreatic and ampullary cancers to standard histopathological variables and survival.

AIM: Angiogenesis is required for tumour growth. Its evaluation, by intratumoural microvessel density (IMD), has prognostic significance in many solid tumours. There is controversy regarding its use in pancreatic cancer and little is known about its role in ampullary tumours. The aim is to study IMD as a prognostic marker in resected ductal adenocarcinomas of head of pancreas and cancers of the ampullary region. METHODS: Forty-seven patients (23 pancreatic and 24 ampullary, mean age 62.0 years) surviving a potentially curative (R0/R1) resection were analysed. Paraffin-embedded sections of these tumours were immunohistochemically stained for CD-34 and IMD was determined (magnification x200). This was correlated with histopathological data and survival using Cox's multivariate analysis. RESULTS: Mean survival for the pancreatic cancer group was 18.4 months (SE=2.7) and 81.2 months (SE=9.9) for the ampullary cancer group. In the pancreatic cancer group, IMD was found to have independent prognostic significance to survival on multivariate analysis (P=0.002, Hazard Ratio (HR) 13.60) along with microscopic resection margin involvement (P=0.003, HR 15.18). For ampullary cancers, IMD was higher in those with lymph node metastasis (P=0.02, Mann-Whitney U -test). CONCLUSION: IMD in resected pancreatic cancers correlates with survival.

Adenocarcinoma↗
PubMed2006

The Rice Annotation Project Database (RAP-DB): hub for Oryza sativa ssp. japonica genome information.

With the completion of the rice genome sequencing, a standardized annotation is necessary so that the information from the genome sequence can be fully utilized in understanding the biology of rice and other cereal crops. An annotation jamboree was held in Japan with the aim of annotating and manually curating all the genes in the rice genome. Here we present the Rice Annotation Project Database (RAP-DB), which has been developed to provide access to the annotation data. The RAP-DB has two different types of annotation viewers, BLAST and BLAT search, and other useful features. By connecting the annotations to other rice genomics data, such as full-length cDNAs and Tos17 mutant lines, the RAP-DB serves as a hub for rice genomics. All of the resources can be accessed through http://rapdb.lab.nig.ac.jp/.

Databases, Nucleic Acid↗
PubMed1999

Patterns of nodal metastases in palpable medullary thyroid carcinoma: recommendations for extent of node dissection.

OBJECTIVE: To establish the frequency, pattern and location of cervical lymph node metastases from palpable medullary thyroid carcinoma (MTC). Recommendations are made regarding the extent of surgery for this tumor. SUMMARY BACKGROUND DATA: Medullary thyroid carcinoma is a tumor of neuroendocrine origin that does not concentrate iodine. Surgical extirpation of the thyroid tumor and cervical node metastases is the only potentially curative therapeutic option. Patterns of node metastases in the neck and guidelines for the extent of dissection for palpable MTC are not well established. METHODS: Seventy-three patients underwent thyroidectomy for palpable MTC with immediate or delayed central and bilateral functional neck dissections. The number and location of lymph node metastases in the central (levels VI and VII) and bilateral (levels II to V) nodal groups were noted and were correlated with the size and location of the primary thyroid tumor. Intraoperative assessment of nodal status by palpation and inspection by the surgeon was correlated with results of histologic examination. RESULTS: Patients with unilateral intrathyroid tumors had lymph node metastases in 81% of central node dissections, 81% of ipsilateral functional (levels II to V) dissections, and 44% of contralateral functional (levels II to V) dissections. In patients with bilateral intrathyroid tumors, nodal metastases were present in 78% of central node dissections, 71% of functional (levels II to V) node dissections ipsilateral to the largest intrathyroid tumor, and 49% of functional (levels II to V) node dissections contralateral to the largest thyroid tumor. The sensitivity of the surgeon's intraoperative assessment for nodal metastases was 64%, and the specificity was 71%. CONCLUSION: In this series, >75% of patients with palpable MTC had associated nodal metastases, which often were not apparent to the surgeon. Routine central and bilateral functional neck dissections should be considered in all patients with palpable MTC.

Adult↗
PubMed2001

Nonablative allogeneic hematopoietic stem cell transplantation.

During the past few years there has been an explosion of knowledge in nonablative allogeneic stem cell transplantation. This approach to transplantation relies more on the creation of "immunologic space" for engraftment rather than the more traditional approach of creating "physical space" by the application of either intensive radiation or chemical therapy. Nonablative allogeneic stem cell transplantation holds the promise of allowing powerful alloimmune responses to eradicate disease processes while minimizing the initial treatment-related morbidity and mortality, and it appears to be the necessary enabling platform by which to apply allogeneic cellular therapy. Intuitively, this approach should broaden the eligibility for potentially curative allogeneic transplantation in various disease categories, reduce initial hospitalization costs, and at the same time have a positive impact on quality of life. We review the current published data relating to this approach including the underlying principles, the preparative regimen, disease indications, preliminary results in hematologic and solid malignancies, and certain correlative immunologic evaluations.

Graft vs Host Disease↗