Use of acupuncture with acupressure in addition to standard-of-care cryotherapy to decrease chemotherapy-associated neuropathy in patients with gastrointestinal malignancies receiving oxaliplatin-based chemotherapy: Study protocol for a randomized, controlled pilot and feasibility study.

BACKGROUND: Oxaliplatin is a key chemotherapeutic agent in the treatment of local and metastatic gastrointestinal (GI) malignancies. Dose density and treatment adherence can be limited by chemotherapy-induced peripheral neuropathy (CIPN). Early research suggests CIPN incidence and severity may be mitigated by acupuncture, but rigorous data in GI oncology patients is limited. Here, we describe the protocol of a randomized, waitlist-controlled pilot study testing the use of preemptive of acupuncture plus acupressure to decrease CIPN and chemotherapy-related toxicities. METHODS: Patients with a GI malignancy (n = 56) with planned 5-fluorouracil (5-FU) and oxaliplatin IV (FOLFOX, FOLFIRINOX) every 2 weeks are being recruited. Additional concurrent anti-neoplastic agents may be used. Enrolled patients are randomized 1:1 to a 3-month intervention of Arm A: acupuncture with acupressure and standard-of-care treatment, or Arm B: standard-of-care alone. In Arm A, on days 1 and 3 of each chemotherapy cycle a standardized acupuncture protocol is administered and patients are taught self-acupressure to perform daily between chemotherapy treatments. Patients in both arms are given standard-of-care oral and peripheral (hands/feet) ice chip cryotherapy during oxaliplatin administration. CIPN and other symptoms are assessed at baseline, 6 weeks, and 3 months from registration. The primary endpoint is CIPN severity at 3 months (EORTC-CIPN 20). Additional endpoints evaluate CIPN incidence (CTCAE, Neuropen, tuning fork); incidence of pain, fatigue, nausea, oral dysesthesia, and anxiety; and feasibility (recruitment, retention, adherence, acceptability). If warranted, trial results will inform the design of a multi-center trial to expand testing of the intervention to a larger patient cohort.

Invasive pulmonary aspergillosis presenting with tracheopleural fistula in a pediatric patient with a history of rhabdomyosarcoma.

Invasive aspergillosis is a known complication in patients with hematologic malignancies. Tracheopleural fistulas are very rare and reported in immunocompromised adults. We present a case of invasive pulmonary aspergillosis with tracheopleural fistula in a pediatric patient with a history of rhabdomyosarcoma and macrophage activation syndrome. This case highlights the importance of recognizing life-threatening fungal infections and coordinating surgical subspecialities for patient care.

Impact of prior alcohol use on the subsequent development of cancer cachexia in male and female mice.

BACKGROUND: Alcohol is a carcinogen and its intake prior to developing cancer and throughout its duration exacerbates cancer cachexia in rodent models. However, the effects on cancer cachexia of stopping alcohol prior to tumor establishment are unknown. METHODS: Male and female mice consumed either a nonalcohol control liquid diet (CON) or a 20% ethanol (kcal/day) liquid diet (EtOH) for 6 weeks. All mice then consumed a control diet and mice in the cancer groups were inoculated with C26 colon cancer cells. Gastrocnemius muscles were collected and analyzed after ~2 weeks. RESULTS: Skeletal muscle weight and male epididymal and female perigonadal fat mass were reduced more by the combination of cancer and prior EtOH than either exposure alone in both males and females. In males, protein synthesis was reduced by 30% following alcohol exposure, while no reductions were observed in female mice. AMPK Thr172 phosphorylation was increased in both male and female EtOH-Cancer groups, while Akt Thr308 phosphorylation was reduced only among males in EtOH-Cancer mice. Substrates in the mTORC1 pathway were reduced by cancer in both males and females, but prior alcohol intake only reduced phosphorylation of 4E-BP1 Ser65 and rpS6 Ser240/244 to a greater extent in male, but not female, mice. Autophagic and proteasomal signaling were largely unaffected by prior alcohol intake in cancer mice, despite a greater increase in Murf1 mRNA in both sexes. CONCLUSIONS: Prior alcohol consumption accelerates or worsens the onset of certain aspects of cancer cachexia in a sex-dependent manner, with males being more sensitive to these exposures, even with abstinence from alcohol prior to tumor initiation.

Paraneoplastic Pemphigus: A Striking Complication of Undiagnosed Lymphoma.

A 49-year-old male with no past medical history presented with acute-onset painful mucosal erosions along with flaccid bullae on his trunk, scalp, and intertriginous areas. The patient initially underwent a skin biopsy which demonstrated suprabasilar acantholysis and lichenoid interface dermatitis. This was followed by a computed tomography scan which identified a large abdominal lymph node. Core needle biopsy of this node demonstrated follicular lymphoma. Lastly, indirect immunofluorescence (IIF) in rat bladder was positive (titer 1 : 10,240). This finding confirmed the diagnosis of paraneoplastic pemphigus (PNP) in the setting of follicular lymphoma. The patient's cutaneous disease was treated with a combination of intravenous immunoglobulin and methylprednisolone, along with intravenous rituximab, with a resolution of his cutaneous symptoms. His lymphoma was treated with six cycles of rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone (R-CHOP), with an interval decrease in his tumor burden. PNP is an autoimmune-mediated mucocutaneous disease associated with underlying neoplasm, most commonly non-Hodgkin lymphoma or chronic lymphocytic leukemia. Affected patients develop variable autoantibodies to antigens on keratinocytes and the basement membrane zone. Severe intractable stomatitis is characteristic, in addition to polymorphous cutaneous eruptions including bullae and erosions. Mortality rates can reach up to 90% due to malignancy, sepsis, or bronchiolitis obliterans, an irreversible and often lethal cause of pulmonary insufficiency. We highlight PNP manifesting in a patient with lymphoma, who responded well to the skin- and malignancy-directed treatments. PNP is an exceedingly rare diagnosis that should be considered in a patient with intractable stomatitis.

Xanthohumol microbiome and signature in adults with Crohn's disease (the XMaS trial): a protocol for a phase II triple-masked, placebo-controlled clinical trial.

BACKGROUND: Xanthohumol (XN), a bioactive flavonoid from Humulus lupulus with anti-inflammatory properties, has potential benefits for patients with Crohn's disease (CD), a type of inflammatory bowel disease. We recently completed and published results of a placebo-controlled phase I clinical trial demonstrating the safety and tolerability of 24 mg XN daily for 8 weeks. The present study aims to evaluate the safety and tolerability of the same dose of XN adults with clinically active CD in a placebo-controlled phase II clinical trial. Additional aims will assess the impact of XN on inflammatory biomarkers, platelet function, CD clinical activity, and stool microbial composition. The metabolism of XN will also be evaluated. This article provides a model protocol for consideration in investigations of XN or other natural products in disease states. METHODS: A triple-masked, randomized, placebo-controlled trial will be conducted in adults with clinically active CD. Participants (n ≤ 32) will be randomized to either 24 mg encapsulated XN per day or placebo and followed for 8 weeks. Throughout the trial, participants will be queried for adverse events. Biomarkers of clinical safety, blood and stool markers of inflammation, platelet function, Crohn's Disease Activity Index score, stool microbial composition, and XN metabolite profiles in blood, urine, and stool will be assessed every 2 weeks. DISCUSSION: We describe the protocol for a phase II clinical trial that evaluates the safety and tolerability of XN in adults with active CD, as well as evaluate metabolism and mechanisms that are relevant to CD and other diseases with underlying inflammation and/or gut permeability. The effects of XN on inflammatory biomarkers, platelet function, the microbiota, and multi-omics biomarkers measured in this phase II trial of adults with CD will be compared to the effects of XN in healthy adults in our previous phase I trial. The results of the study will advance the evidence guiding the use of XN in patients with CD. TRIAL REGISTRATION: ClinialTrials.gov NCT04590508. Registered on October 19, 2020.

Risk Factors for 30-day and 90-day Readmission After Lumbar Decompression.

STUDY DESIGN: Retrospective cohort study. OBJECTIVE: To assess readmission rates and risk factors for 30-day and 90-day readmission after elective lumbar decompression at a single institution. SUMMARY OF BACKGROUND DATA: Hospital readmission is an undesirable aspect of interventional treatment. Studies evaluating readmissions after elective lumbar decompression typically analyze national databases, and therefore have several drawbacks inherent to their macroscopic nature that limit their clinical utility. METHODS: Patients undergoing primary one- to four-level lumbar decompression surgery were retrospectively identified. Demographic, surgical, and readmission data within "30-days" (0-30 days) and "90-days" (31-90 days) postoperatively were extracted from electronic medical records. Patients were categorized into four groups: (1) no readmission, (2) readmission during the 30-day or 90-day postoperative period, (3) complication related to surgery, and (4) Emergency Department (ED)/Observational (OBs)/Urgent (UC) care. RESULTS: A total of 2635 patients were included. Seventy-six (2.9%) were readmitted at some point within the 30- (2.3%) or 90-day (0.3%) postoperative periods. Patients in the pooled readmitted group were older (63.1 yr, P  < 0.001), had a higher American Society of Anesthesiologists (ASA) grade (31.2% with ASA of 3, P = 0.03), and more often had liver disease (8.1%, P = 0.004) or rheumatoid arthritis (12.0%, P = 0.02) than other cohorts. A greater proportion of 90-day readmissions and complications had surgical-related diagnoses or a diagnosis of recurrent disc herniation than 30-day readmissions and complications (66.7% vs. 44.5%, P = 0.04 and 33.3% vs. 5.5%, P < 0.001, respectively). Age (Odds ratio [OR]: 1.02, P = 0.01), current smoking status (OR: 2.38, P < 0.001), longer length of stay (OR: 1.14, P < 0.001), and a history of renal failure (OR: 2.59, P = 0.03) were independently associated with readmission or complication. CONCLUSION: Increased age, current smoking status, hospital length of stay, and a history of renal failure were found to be significant independent predictors of inpatient readmission or complication after lumbar decompression.

Xanthohumol microbiome and signature in healthy adults (the XMaS trial): a phase I triple-masked, placebo-controlled clinical trial.

BACKGROUND: Natural products may provide a source for the discovery and development of adjunctive pharmacological interventions to modulate the inflammatory pathways contributing to chronic disease. Xanthohumol, a flavonoid from the hops plant (Humulus lupulus), has antioxidant and anti-inflammatory properties and may act as a prebiotic to the intestinal microbiota. Xanthohumol is not currently approved as a drug by the US Food and Drug Administration (FDA), but is available as a dietary supplement and ingredient in medical foods. To formally test the safety of xanthohumol, a phase I clinical trial ("XMaS") was designed and approved under an Investigational New Drug application to the US FDA. The main objective is to examine the clinical safety and subjective tolerability of xanthohumol in healthy adults compared to placebo. Additional aims are to monitor biomarkers related to inflammation, gut permeability, bile acid metabolism, routes, and in vivo products of xanthohumol metabolism, and to evaluate xanthohumol's impact on gut microbial composition. METHODS: The safety and tolerability of xanthohumol in healthy adults will be evaluated in a triple-masked, randomized, placebo-controlled trial. Participants will be randomized to either 24 mg/day of xanthohumol or placebo for 8 weeks. Blood cell counts, hepatic and renal function tests, electrolytes, and self-reported health-related quality of life measures will be collected every 2 weeks. Participants will be queried for adverse events throughout the trial. Xanthohumol metabolites in blood, urine, and stool will be measured. Biomarkers to be evaluated include plasma tumor necrosis factor-alpha, various interleukins, soluble CD14, lipopolysaccharide-binding protein, fecal calprotectin, and bile acids to assess impact on inflammatory and gut permeability-related mechanisms in vivo. Stool samples will be analyzed to determine effects on the gut microbiome. DISCUSSION: This phase I clinical trial of xanthohumol will assess safety and tolerability in healthy adults, collect extensive biomarker data for assessment of potential mechanism(s), and provide comparison data necessary for future phase II trials in chronic disease(s). The design and robustness of the planned safety and mechanistic evaluations planned provide a model for drug discovery pursuits from natural products. TRIAL REGISTRATION: ClinicalTrials.gov NCT03735420 . Registered on November 8, 2018.

Renal biopsy under augmented reality guidance.

Kidney biopsies are currently performed using preoperative imaging to identify the lesion of interest and intraoperative imaging used to guide the biopsy needle to the tissue of interest. Often, these are not the same modalities forcing the physician to perform a mental cross-modality fusion of the preoperative and intraoperative scans. This limits the accuracy and reproducibility of the biopsy procedure. In this study, we developed an augmented reality system to display holographic representations of lesions superimposed on a phantom. This system allows the integration of preoperative CT scans with intraoperative ultrasound scans to better determine the lesion's real-time location. An automated deformable registration algorithm was used to increase the accuracy of the holographic lesion locations, and a magnetic tracking system was developed to provide guidance for the biopsy procedure. Our method achieved a targeting accuracy of 2.9 ± 1.5 mm in a renal phantom study.

A complex dual-modality kidney phantom for renal biopsy studies.

We developed a reliable and repeatable process to create hyper-realistic, kidney phantoms with tunable image visibility under ultrasound (US) and CT imaging modalities. A methodology was defined to create phantoms that could be produced for renal biopsy evaluation. The final complex kidney phantom was devised containing critical structures of a kidney: kidney cortex, medulla, and ureter. Simultaneously, some lesions were integrated into the phantom to mimic the presence of tumors during biopsy. The phantoms were created and scanned by ultrasound and CT scanners to verify the visibility of the complex internal structures and to observe the interactions between material properties. The result was a successful advancement in knowledge of materials with ideal acoustic and impedance properties to replicate human organs for the field of image-guided interventions.

Sweat Testing in Ireland

Introduction Quick, painless, cheap and reliable, the sweat test remains the gold standard diagnostic test for cystic fibrosis. We aimed to describe the pattern of testing in Ireland over a calendar year. Methods Information on sweat test practices was requested from each centre between 1st January 2011 and 31st December 2011, and the number of positive, negative, equivocal, and insufficient samples was recorded. Results In 2011 there were 2555 sweat tests performed in 15 centres, ranging from 35 to over 450 tests per centre. 35 (1.4%) were in the diagnostic range. The overall quantity not sufficient (QNS) rate was 10.3% (range 0-28.3%). Testing was performed across a wide age range (2.5 weeks to 75 years). The mean sweat chloride value was 16.5 mmol/L (SD 16.1 mmol/L). Discussion Our study demonstrates a high number of sweat tests performed in Ireland with significant variation in sweat testing practices across 15 different sites.

Stability and accuracy of total and free PSA values in samples stored at room temperature.

INTRODUCTION: In 2010, an estimated 476,076 total PSA tests were performed in Ireland, at a cost of €3.6 million with the majority ordered by general practitioners. We aimed to replicate storage conditions at room temperature and see if prolonged storage affected total and free PSA values. METHODS: Blood samples were taken from 20 male patients in four VACUETTE® Serum Separator tubes (Greiner-Bio-One, Austria) and stored at room temperature (22 °C) for different time intervals (4, 8, 24, 48 h) before being centrifuged and analyzed. Total PSA (tPSA) and free PSA (fPSA) values were determined using the Tosoh AIA 1800 assay (Tokyo, Japan). RESULTS: Mean tPSA values were measured at 4, 8, 24 and 48 h with values of 7.9, 8.1, 7.8 and 8.0 µg/L, respectively. Values ranged from -1.26 to +2.53 % compared to the initial 4 h interval reading, indicating tPSA remained consistent at room temperature. The tPSA showed no significance between groups (ANOVA, p = 0.283). Mean fPSA values at 4, 8, 24 and 48 h were 2.05, 2.04, 1.83, 1.82 µg/L, respectively. At 24 and 48 h there was 10.73 and 11.22 % reduction, respectively, in fPSA compared to the 4-h time interval, indicating prolonged storage resulted in reduced fPSA values. After 24 h, there was an 8.8 % reduction in the free/total PSA %. The fPSA showed significant differences between groups (ANOVA, p = 0.024). CONCLUSIONS: Our recommendation is that samples that have been stored for prolonged amounts of time (greater than 24 h) should not be used for free PSA testing.