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1.
Chest ; 162(4):A1000, 2022.
Article in English | EMBASE | ID: covidwho-2060747

ABSTRACT

SESSION TITLE: Shock and Sepsis in the ICU Case Posters SESSION TYPE: Case Report Posters PRESENTED ON: 10/19/2022 12:45 pm - 01:45 pm INTRODUCTION: Nocardiosis is a rare bacterial infection, which frequently affects immunocompromised patients. It can present as an acute, subacute, or chronic pulmonary infection with non-specific symptoms, such as fever, cough, dyspnea, weight loss, and hemoptysis. CASE PRESENTATION: A 34-year-old female with a history of chronic granulomatous disease and hidradenitis suppurativa on adalimumab presented to the ED with fever, shortness of breath, and productive cough of 2 days. Her vitals were T 101F, BP 66/48, HR 148, RR 42, and SPO2 94% on room air. On exam, she was cachectic, with bilateral crackles and rales in the right lung base. Extremities were cold, with trace pitting edema was present on bilateral lower extremities. COVID-19 PCR was negative. Despite fluid resuscitation, she remained hypotensive and was started on norepinephrine. Blood cultures were collected, and broad-spectrum antibiotics and an antifungal agent were initiated. Chest CT demonstrated bilateral multifocal consolidation with surrounding ground-glass opacities and complete consolidation of the right lower lobe. Due to worsening respiratory distress and tachypnea, and lack of improvement with non-invasive ventilation, she was intubated, placed on mechanical ventilation, and admitted to the Medical ICU. On hospital day 1, due to the patient's immunosuppression, unresolving shock, and radiographic findings, a bronchoscopy with bronchoalveolar lavage (BAL) was performed. On hospital day 2, a transthoracic echocardiogram showed LV ejection fraction of 20-25% with severe global hypokinesis of the LV. ACS workup had been unremarkable, with mildly elevated troponin and no ischemic changes on EKG. She was initiated on cardiac inotropes. On hospital day 3, BAL culture revealed Nocardia cyriacigeorgica. TMP-SMX and ceftriaxone were started for severe pulmonary nocardiosis. On hospital day 11, she was liberated from mechanical ventilation, and by hospital day 14, she was weaned off all pressors and inotropes. Approximately 4 weeks after admission, repeat TTE showed recovery of LV ejection fraction (55-60%) and she was discharged with a prolonged course of TMP-SMX and IV ceftriaxone, with duration to be determined at outpatient infectious disease follow-up. DISCUSSION: We discuss a unique case of severe pulmonary nocardiosis, presenting with ARDS and cardiogenic shock. To the best of our knowledge, this is the first case of a patient with pulmonary nocardiosis presenting with stress cardiomyopathy reported in the literature. While the pathophysiology is not well understood, theorized mechanisms include catecholamine excess, coronary artery spasm, microvascular dysfunction. CONCLUSIONS: This case highlights the need for a broad differential diagnosis in patients presenting with ARDS and cardiogenic shock and illustrates the value of clinical bronchoscopy in patients with unique presenting features. Reference #1: Lerner PI. Nocardiosis. Clin Infect Dis. 1996 Jun;22(6):891-903;quiz 904-5. doi: 10.1093/clinids/22.6.891. PMID: 8783685. Reference #2: Wittstein IS, Thiemann DR, Lima JA, Baughman KL, Schulman SP, Gerstenblith G, Wu KC, Rade JJ, Bivalacqua TJ, Champion HC. Neurohumoral features of myocardial stunning due to sudden emotional stress. N Engl J Med. 2005 Feb 10;352(6):539-48. doi: 10.1056/NEJMoa043046. PMID: 15703419. Reference #3: Park JH, Kang SJ, Song JK, Kim HK, Lim CM, Kang DH, Koh Y. Left ventricular apical ballooning due to severe physical stress in patients admitted to the medical ICU. Chest. 2005 Jul;128(1):296-302. doi: 10.1378/chest.128.1.296. PMID: 16002949. DISCLOSURES: no disclosure on file for D. Clark Files;No relevant relationships by Nisha Patel No relevant relationships by Meehir Shah

2.
Clinical Nutrition ESPEN ; 48:502, 2022.
Article in English | EMBASE | ID: covidwho-2003957

ABSTRACT

Patients recovering from COVID-19 infection are at a high risk of malnutrition, reduced nutritional intake and decline in muscle mass and strength.1 The aim of this service evaluation is to describe baseline characteristics, quantify risk of malnutrition, provide an overview of nutritional status and nutritional related outcomes for patients recovering post COVID-19 infection on rehabilitation wards. Data collection occurred between the 1st of February and the 1st of July 2021. This cohort included all patients who were recovering from COVID-19, who were referred to dietetic service and transferred to a rehabilitation ward. Demographic data and nutritional parameters were gathered from electronic records, and dietetic assessments. A total of 54 patients were included: 59% male, 41% female. Ages ranged from 46 to 95 years with average age of 79.9 years and average length of hospital stay of 92 days. One fifth of those included had an ICU stay. Where data was available on sarcopenia risk, 50% were identified as at risk of sarcopenia. Of those where serum 25-hydroxyvitamin D was checked, 45% had insufficient vitamin D levels. A nutrition focused physical exam was completed for 18 patients (one third of the cohort). Using this exam, 61% were diagnosed with moderate or severe malnutrition. At least 15% of patients experienced significant weight loss between their admission to the hospital compared to their weight on admission to post COVID-19 rehabilitation ward. Of those where Malnutrition Screening Tool was completed on admission to COVID-19 rehabilitation ward, 33% were identified as at risk of malnutrition. On discharge from the dietetic caseload, the proportion of those identified at risk of malnutrition using this tool decreased to 18%. During the period from admission to COVID-19 rehabilitation ward and discharge from dietetic service, 42% gained weight, 54% maintained their weight, 4% lost weight. Of those with data available regarding nutritional intake on admission to COVID-19 rehabilitation ward, 28% met energy requirements and 44% met protein requirements. On discharge from dietetic service these proportions increased to 66% meeting energy requirements and 74% meeting protein requirements. The average kcal intake on admission to COVID-19 rehabilitation increased from 1531kcal to 1778kcal on discharge and the average protein intake increased from 67g on admission to post COVID-19 rehabilitation to 75g on discharge. These results demonstrate the high prevalence of malnutrition and high risk of sarcopenia in patients admitted for rehabilitation post COVID-19 infection. With dietetic input, improvements were observed in patient’s nutritional intake, and nutritional outcomes such as weight and malnutrition risk. These results illustrate the need for early dietetic input in those recovering post COVID-19 infection to optimise nutritional status and nutritional outcomes. References: 1. Anker M. S., Landmesser U., von Haehling S et al. Weight loss, malnutrition, and cachexia in COVID-19: facts and numbers. Journal of Cachexia, Sarcopenia and Muscle, 12, 9– 13.

3.
American Journal of Kidney Diseases ; 79(4):S37-S38, 2022.
Article in English | EMBASE | ID: covidwho-1996885

ABSTRACT

Cocaine is one of the most used illicit drugs. Cocaine induced toxicity can result in hepatotoxicity, pulmonary toxicity, and renal dysfunction. Acute kidney injury (AKI) is an emergent complication in cocaine abusers. Rhabdomyolysis and vasoconstrictions mechanism are well known cause of AKI, cocaine induce thrombotic microangiopathy (TMA) is rarely reported. Cocaine is widely used in the United States, we report a case of Cocaine induced TMA in a cocaine abuser. We chronicle a case of a 42-Year-old male cocaine abuser, who presented to ED with complaints of Dyspnea, cough, anorexia and chest tightness for two days. He attributed to inhaling ammonia from cat urine along with cocaine abuse. No prior history of kidney disease or any other chronic illness. On examination, the patient appeared malnourished and cachectic. He was normotensive, lethargic and oriented. There were crackles at the lung bases. Blood tests revealed serum creatinine 18.0 mg/dL, blood urea nitrogen 150 mg/dL, hemoglobin 8.2 g/dL, platelets 173000/mm3, Retics count 8 %, LDH 1120 (84–246 IU/L) and haptoglobin < 8 (30–200mg/dL). A blood film revealed occasional schistocytes. Urinalysis showed proteinuria and microscopic hematuria. Urine toxicology revealed cocaine. Routine blood and urine cultures showed no growth. Serologic tests showed reduced complement C3 level of 40 (82-185 mg/dL) and normal C4 level of 32 (10–53mg/dL). There were no antibodies against HIV 1/2 and Covid 19. His ADAMTS-13 results showed 0.61 and 0.63 (0.68 to 1.63). Renal Ultrasound was unremarkable. Patient was intubated and ventilated in ICU;he was initiated on hemodialysis. He was provided four sessions of plasma exchanges till his ADAMTS-13 result came back near normal that was indicative of Cocaine induce TMA. Cocaine abuse is a global issue with increasing number of cases in the USA. It can cause AKI due to well-known etiologies like Rhabdomyolysis, Vasculitis, Acute interstitial Nephritis and Renal Infarction. However, Clinicians and nephrologists should also consider rare causes like TMA as a possible differential cause of AKI in the setting of cocaine abuse.

4.
Journal of General Internal Medicine ; 37:S521, 2022.
Article in English | EMBASE | ID: covidwho-1995801

ABSTRACT

CASE: A 25-year-old homeless male with nonadherent HIV presented with dyspnea on exertion for 4 days, productive cough for 1 week, fevers, chills and night sweats. He arrived hypoxic to 74% requiring 2L O2 and was cachectic on exam. WBC, lactate and procalcitonin were normal. C-reactive protein was 26.7 mg/L, LDH was 686 units/L and COVID-19 was positive. An arterial blood gas showed a primary respiratory alkalosis with a secondary metabolic alkalosis. Computed tomography of the chest, abdomen and pelvis with contrast showed multifocal large thin-walled cavitary lesions throughout the bilateral lungs with subpleural large cystic disease. Dexamethasone, remdesivir and empiric antibiotics were initiated. Absolute CD4 count was 7 cells/uL with HIV-1 RNA load of 139,000 copies/mL. Sputum was positive for Pneumocystis jirovecii (PCP) by DFA and PCR, but no evidence of mycobacterium. Trimethoprim-sulfamethoxazole (TMP-SMX) was added. On hospital day 13, he developed severe right-sided chest pain, dyspnea and required up to 15L O2. A chest x-ray revealed a large right-sided pneumothorax (PTX) and a chest tube was placed. Cardiothoracic Surgery was consulted for consideration of bullectomy with pleurodesis;this was not recommended as the cystic lesions were extensive with some intraparenchymal. His oxygen requirements improved and his chest tube was removed in 6 days. He was discharged on hospital day 21 to begin prophylactic dosing of TMP-SMX until his CD4 count was over 200 cells/uL and to attend his first appointment at an outpatient HIV clinic the following day. IMPACT/DISCUSSION: Secondary spontaneous pneumothorax (SSP) can be a complication of necrotizing pneumonia due to PCP. In one study, in a cohort of 599 patients with HIV infection, only 1.2% developed a PTX. Bilateral PTX is more common with PCP, unlike in our patient. In HIV, the degree of immunosuppression can influence the cause of PTX. Our patient had a PTX with a CD4 count under 200, which is more common with PCP. In addition, SSP as a complication of SARS-CoV-2 is more rare. There are case series that describe COVID-19 patients who develop PTX in the absence of barotrauma secondary to mechanical ventilation. However, this is uncommon as one retrospective study reports PTX occurring in 1% of patients with COVID-19 requiring hospital admission. In this case, it is unclear to what extent the patient's concomitant COVID-19 contributed to the development of a PTX. Our patient was ineligible for definitive intervention to prevent recurrence, thus underwent tube thoracostomy placement which is consistent with the majority of treated patients. While the prognosis of PTX secondary to COVID-19 is generally good, prognosis of cominant co-infection with PCP is an area of further research as the overall mortality of PCP-induced PTX alone can be 23%. CONCLUSION: This case represents a rare occurrence of spontaneous pneumothorax secondary to both PCP and COVID-19. We suggest the incidence to increase as the pandemic continues.

5.
Journal of General Internal Medicine ; 37:S381, 2022.
Article in English | EMBASE | ID: covidwho-1995664

ABSTRACT

CASE: A 51-year-old man without significant past medical history presented to our hospital with dyspnea on exertion. SARS-CoV-2 was detected on routine occupational screening 2 months prior to admission. He subsequently reported a 100lb weight loss, during which time he experienced dysgeusia and ate primarily cereal, sandwiches, and potatoes and consumed nearly no fruits or vegetables. Three weeks prior to admission he developed postprandial nausea and vomiting and anorexia. A week later he developed progressive epigastric pain, lower extremity edema, and dyspnea while walking around the college campus where he worked as a security guard, and sought medical attention. He did not have fever, chills, night sweats, cough, orthopnea, paroxysmal nocturnal dyspnea, rash, or diarrhea. He had not seen a doctor in 20 years and took no medications. He did not drink alcohol, smoke cigarettes, or use illicit substances. Vital signs were T 36.6°F HR 104 BP 149/111 RR 20 and SpO2 97%. Physical examination revealed a cachectic man with bitemporal wasting, sunken orbits, poor dentition, and severe periodontal disease. JVP was 14cm of H2O at 45°. An S3 was present. The abdomen was tender to palpation in the mid epigastrium. The extremities were cool with 3+ pitting edema. Pancreatitis was diagnosed after discovery of markedly elevated lipase levels and peripancreatic fat stranding on abdominal CT. TTE showed biventricular systolic dysfunction with LVEF 15%. He developed cardiogenic shock complicated by oliguric renal failure, congestive hepatopathy and obtundation, requiring ICU transfer for diuresis and inotropic support. Further workup revealed deficiencies of thiamine, zinc, and vitamins A, C, and D. A regadenoson myocardial perfusion PET/CT showed no flow-limiting coronary artery disease, and workup for inflammatory, infectious, and toxic-metabolic causes of heart failure was unrevealing. While COVID myocarditis and multisystem inflammatory syndrome in adults (MIS-A) were considered, ultimately, a diagnosis of wet beriberi was made. After 5 months of aggressive nutritional supplementation via percutaneous gastrostomy tube and initiation of guideline-directed medical therapy, LVEF improved to 53% and weight increased by 35lbs. IMPACT/DISCUSSION: Wet beriberi is a potentially underrecognized cause of dilated cardiomyopathy in resource-rich areas. Within 3 months, thiamine deficiency can cause high-output heart failure due to impaired myocardial energy metabolism and dysautonomia. Risk factors include alcohol use disorder, prolonged vomiting, and history of bariatric surgery. CONCLUSION: The laboratory evaluation of non-ischemic dilated cardiomyopathy should include measurement of serum thiamine, carnitine, and selenium levels in select patients, alongside iron studies, ANA, screening for HIV, Chagas disease, and viral myocarditis, and genetic testing in patients with a suggestive family history. Empiric thiamine repletion should be considered in all critically ill patients with evidence of malnutrition.

6.
Cells ; 11(15)2022 Jul 25.
Article in English | MEDLINE | ID: covidwho-1993936

ABSTRACT

Skeletal muscle is a pivotal organ in humans that maintains locomotion and homeostasis. Muscle atrophy caused by sarcopenia and cachexia, which results in reduced muscle mass and impaired skeletal muscle function, is a serious health condition that decreases life longevity in humans. Recent studies have revealed the molecular mechanisms by which long non-coding RNAs (lncRNAs) regulate skeletal muscle mass and function through transcriptional regulation, fiber-type switching, and skeletal muscle cell proliferation. In addition, lncRNAs function as natural inhibitors of microRNAs and induce muscle hypertrophy or atrophy. Intriguingly, muscle atrophy modifies the expression of thousands of lncRNAs. Therefore, although their exact functions have not yet been fully elucidated, various novel lncRNAs associated with muscle atrophy have been identified. Here, we comprehensively review recent knowledge on the regulatory roles of lncRNAs in skeletal muscle atrophy. In addition, we discuss the issues and possibilities of targeting lncRNAs as a treatment for skeletal muscle atrophy and muscle wasting disorders in humans.


Subject(s)
Muscular Diseases , RNA, Long Noncoding , Humans , Muscle Development/genetics , Muscle, Skeletal/metabolism , Muscular Atrophy/genetics , Muscular Atrophy/metabolism , Muscular Diseases/genetics , RNA, Long Noncoding/genetics , RNA, Long Noncoding/metabolism
7.
Journal of Forensic Medicine and Toxicology ; 39(1):129-132, 2022.
Article in English | EMBASE | ID: covidwho-1988394

ABSTRACT

Tuberculosis (TB) is a communicable bacterial infection caused by Mycobacterium tuberculosis. It is the second leading fatal infectious disease after COVID-19. Tuberculosis also stands at 13th position, with respect to the leading cause of death. In 2020, around 86% of new tuberculosis cases were reported in 30 countries, of which two-thirds of cases were recorded in eight countries alone, with India leading the chart. Tuberculosis in a mentally ill patient is a common entity because of its common comorbidities, but prolonged antipsychotic drug therapy is rare. Here we discuss a case of a 36 years old female who was brought dead to casualty. She was apparently alright 10 days back and then developed symptoms like fever, breathlessness, and cough. She had severe anorexia and cachexia for the past few months. She has been under antipsychotic medication for schizophrenia. On autopsy, there were multiple whitish nodules present all over the intestine and various abdominal organs. We identified disseminated tuberculosis, and we analyzed histopathology and microbiology of tissues. We reported Ziehl-Neelsen staining negative for TB. Culture reported positive for Mycobacterium tuberculosis. Histopathology study tissues showed caseous necrotizing granulomas. As seen in some literature, tuberculosis can be seen in mentally ill patients, whereas literature showing the association between tuberculosis and antipsychotic drugs is less. This article highlights the association between such occurrence of tuberculosis while undertaking antipsychotic drug therapy.

8.
Annals of Oncology ; 33:S375-S376, 2022.
Article in English | EMBASE | ID: covidwho-1936046

ABSTRACT

Background: Despite the occurrence of HER2 amplification/overexpression (HER2+) in ~3% to 5% of all patients with metastatic colorectal cancer (mCRC) and up to ~10% of patients with RAS/BRAF wild-type mCRC, there are currently no FDA- or EMA-approved HER2-directed therapies for HER2+ mCRC. Patients with mCRC who progress on early lines of chemotherapy regimens receive limited clinical benefit from current standard-of-care treatments. Tucatinib is a highly selective, HER2-directed, tyrosine kinase inhibitor. The MOUNTAINEER trial (NCT03043313) was initiated to evaluate the efficacy and safety of the investigational combination of tucatinib with trastuzumab in patients with HER2+ mCRC. Here we present results from the primary analysis of MOUNTAINEER. Methods: MOUNTAINEER is a multi-center, open-label, randomised, phase 2 trial conducted in the US and Europe. Eligible patients had HER2+ (one or more local tests: 3+ immunohistochemistry, 2+ immunohistochemistry with amplification by in situ hybridization, or amplification by next‑generation sequencing of tumor tissue) and RAS wild-type mCRC with progression on or intolerance to fluoropyrimidine, oxaliplatin, irinotecan, and an anti-VEGF antibody. Measurable disease and an ECOG performance status of 0–2 were required. Previous HER2-directed therapies were not permitted. The trial initially consisted of a single cohort (Cohort A) to be treated with tucatinib (300 mg PO BID) and trastuzumab (8 mg/kg IV then 6 mg/kg IV every 3 weeks). The trial was expanded to include patients randomised 4:3 to receive tucatinib + trastuzumab (Cohort B) or tucatinib monotherapy (Cohort C). The primary endpoint is confirmed objective response rate (ORR) per RECIST 1.1 by blinded independent central review (BICR) in Cohorts A+B. Secondary endpoints include duration of response (DOR), progression-free survival (PFS), overall survival (OS), and safety and tolerability. Results: MOUNTAINEER enrolled 117 patients between 08Aug2017 and 22Sept2021. Data cutoff was 28Mar2022. The median age was 56.0 years (range, 24, 77), and baseline characteristics were balanced across cohorts. Eighty-six patients received at least 1 dose of study treatment in Cohorts A+B, and 30 patients received tucatinib monotherapy in Cohort C (total, 116). The overall median duration of follow-up was 16.3 months (IQR, 10.8, 28.2). In Cohorts A+B, the confirmed ORR by BICR was 38.1% (95% CI, 27.7, 49.3). The median DOR was 12.4 months (95% CI, 8.5, 20.5). The median PFS was 8.2 months (95% CI, 4.2, 10.3), and the median OS was 24.1 months (95% CI, 20.3, 36.7). The most common adverse events (AEs) in Cohorts A+B were diarrhoea (64.0%), fatigue (44.2%), nausea (34.9%), and infusion-related reaction (20.9%);the most common AE of grade ≥3 was hypertension (7.0%). Adverse events leading to tucatinib discontinuation in Cohorts A+B occurred in 5.8% of patients and included alanine amino transferase increase (2.3%), COVID-19 pneumonia (1.2%), cholangitis (1.2%), and fatigue (1.2%). No deaths resulted from AEs. Conclusions: In patients with chemotherapy-refractory HER2+ mCRC, tucatinib in combination with trastuzumab was well tolerated with clinically meaningful antitumor activity including durable responses and a median overall survival of 2 years. Tucatinib in combination with trastuzumab has the potential to become a new standard of care for patients with HER2+ mCRC. Clinical trial identification: NCT03043313. Editorial acknowledgement: The authors thank Joseph Giaconia of MMS Holdings, Michigan, USA for providing medical writing support/editorial support, which was funded by Seagen Inc., Bothell, WA, USA in accordance with Good Publication Practice (GPP3) guidelines. Legal entity responsible for the study: Seagen Inc. Funding: Seagen Inc. Disclosures: J. Strickler: Advisory / Consultancy: Seagen, Bayer, Pfizer;Research grant / Funding (institution): Amgen, Roche/Genentech, Seagen. A. Cercek: Advisory / Consultancy: Bayer, Merck, Seagen;Research grant / Funding (institution): Seagen, GSK, Rgenix. T. André: Honoraria (self : Amgen, Astra-Zeneca, Bristol-Myers Squibb, Gritstone Oncology, GlaxoSmithKline, Haliodx, Kaleido Biosciences, Merck & Co., Inc., Pierre Fabre, Sanofi, Servier, Merck & Co., Inc, Servier;Advisory / Consultancy: Astellas Pharma, BMS, Gritstone Oncology, Transgène, Roche/Ventana, Seagen, Merck & Co., Inc, Servier;Research grant / Funding (institution): BMS, Seagen, GSK;Travel / Accommodation / Expenses: BMS, Merck & Co., Inc. K. Ng: Advisory / Consultancy: Seattle Genetics, Bicara Therapeutics, GlaxoSmithKline;Research grant / Funding (institution): Pharmavite, Evergrande Group, Janssen. E. Van Cutsem: Advisory / Consultancy: AbbVie, Array, Astellas, AstraZeneca, Bayer, Beigene, Biocartis, Boehringer Ingelheim, Bristol-Myers Squibb, Celgene, Daiichi, Halozyme, GSK, Helsinn, Incyte, Ipsen, Janssen Research, Lilly, Merck Sharp & Dohme, Merck KGaA, Mirati, Novartis, Pierre Fabre, Roche, Seattle Genetics, Servier, Sirtex, Terumo, Taiho, TRIGR, Zymeworks;Research grant / Funding (institution): Amgen, Bayer, Boehringer Ingelheim, Bristol-Myers Squibb, Celgene, Ipsen, Lilly, Merck Sharp & Dohme, Merck KGaA, Novartis, Roche, Servier. C. Wu: Research grant / Funding (institution): Seagen. A. Paulson: Research grant / Funding (institution): Seattle Genetics. J. Hubbard: Research grant / Funding (institution): Seattle Genetics. H. Lenz: Honoraria (self): BMS, Bayer, Roche;Advisory / Consultancy: Bayer, Merck, Roche;Travel / Accommodation / Expenses: BMS, Bayer, Merck KG;Shareholder / Stockholder / Stock options: Fulgent. M. Stecher: Full / Part-time employment: SeaGen. W. Feng: Full / Part-time employment: Seagen. T. Bekaii-Saab: Honoraria (self): Royalties: Uptodate;Advisory / Consultancy: Consulting (to institution): Ipsen, Arcus, Pfizer, Seattle Genetics, Bayer, Genentech, Incyte, Eisai and Merck., Consulting (to self): Stemline, AbbVie, Boehringer Ingelheim, Janssen, Daichii Sankyo, Natera, TreosBio, Celularity, Exact Science, Sobi, Beigene, Kanaph, Astra Zeneca, Deciphera, MJH Life Sciences, Aptitude Health, Illumina and Foundation Medicine, IDMC/DSMB: Fibrogen, Suzhou Kintor, Astra Zeneca, Exelixis, Merck/Eisai, PanCan and 1Globe;Research grant / Funding (institution): Agios, Arys, Arcus, Atreca, Boston Biomedical, Bayer, Eisai, Celgene, Lilly, Ipsen, Clovis, Seattle Genetics, Genentech, Novartis, Mirati, Merus, Abgenomics, Incyte, Pfizer, BMS.;Licensing / Royalties: WO/2018/183488: HUMAN PD1 PEPTIDE VACCINES AND USES THEREOF – Licensed to Imugene, WO/2019/055687: METHODS AND COMPOSITIONS FOR THE TREATMENT OF CANCER CACHEXIA – Licensed to Recursion. All other authors have declared no conflicts of interest.

9.
American Journal of Respiratory and Critical Care Medicine ; 205(1), 2022.
Article in English | EMBASE | ID: covidwho-1927721

ABSTRACT

Introduction: First synthesized in 1869, Hydroxyurea is known for its efficacy in treating myeloproliferative disorders, cervical cancer, and sickle cell disease. Usually well-tolerated, Hydroxyurea has numerous documented adverse effects, including bone marrow suppression, fevers, gastrointestinal upset, anorexia, and maculopapular rash. In addition, one rare side effect is interstitial pneumonitis, a potentially devastating complication if overlooked. We present one such case of Hydroxyurea-induced interstitial pneumonitis. Case Description: A 65-year-old man with a six-month diagnosis of Chronic Granulocytic Leukemia (CGL) on Hydroxyurea developed acute hypoxemic respiratory failure saturating 80% on room air with HR 102, RR 24, and increasing oxygen requirements (10 Lpm) after being admitted with complaints of worsening dyspnea, fatigue, and productive cough with yellow/green sputum. Physical examination was notable for cachexia, ill appearance, generalized weakness, hoarse voice, tachycardia, tachypnea, diffusely diminished breath sounds, and scattered rales on auscultation of lung fields. Initial imaging was notable for bilateral airspace disease and pulmonary opacities on chest radiography and bilateral pneumonia (concerning for COVID-19 pneumonia), mediastinal adenopathy, and splenomegaly on chest computed tomography. Initial laboratory results were notable for leukocytosis 62.5 th/uL, lactic acidosis 2.5 mmol/L, procalcitonin level 4.95 ng/mL, and negative COVID-19 PCR test. Prompt initiation of Vancomycin/Cefepime therapy ensued upon collection of blood cultures in light of possible sepsis. Flagyl, Valacyclovir, and Posaconazole were added to antimicrobial coverage, along with steroid therapy, due to minimal clinical improvement. Tachycardia with significant oxygen requirements alternating between BiPAP and heated high flow nasal cannula with FiO2 ranging from 70-85% persisted. Daily imaging also showed worsening airspace disease. Negative viral, bacterial, and fungal cultures led to subsequent discontinuation of Hydroxyurea therapy due to suspicion of medicationinduced pneumonitis. Three days after cessation of Hydroxyurea, the patient's oxygen requirements began to decrease and imaging revealed interval resolution of pneumonitic changes in the absence of antimicrobial therapy. The patient was later transitioned to Ruxolitinib for his underlying CGL prior to his discharge home without the need for home oxygen therapy. Discussion: Thought to be caused by hypersensitivity pneumonitis, pulmonary toxicity from Hydroxyurea can easily be misdiagnosed. Unfortunately, while much is known about the pancytopenic, gastrointestinal, and cutaneous side effects of Hydroxyurea, few cases in the literature highlight the potentially fatal interstitial pneumopathy caused by Hydroxyurea, first reported in 1999. Thus, this case serves as an additional contribution to the minutiae of literature detailing Hydroxyurea's adverse pulmonary side effect profile. (Figure Presented).

10.
BMC Palliative Care ; 21:1-17, 2022.
Article in English | ProQuest Central | ID: covidwho-1856996

ABSTRACT

Cachexia is a prevalent muscle wasting syndrome among people with advanced cancer that profoundly impacts patient quality of life (QoL) and physical function. Exercise can improve QoL, physical function, and overall health in people with cancer and may be an important addition to treatment approaches for cancer cachexia. Greater understanding of patients’ perception of exercise can help elucidate the feasibility of implementing exercise interventions for cancer cachexia and facilitate the design of patient-centered interventions. We aimed to describe the perception of exercise in patients with advanced cancer and cachexia, and capture exercise motivators, barriers, and preferences, to inform the feasibility of exercise interventions. Individual interviews (n = 20) with patients with locally advanced or metastatic cancer with cachexia were conducted and analyzed using reflexive thematic analysis. Main themes from interviews were: 1) Life is disrupted by cancer and cachexia;2) Exercise offers hope;3) Exercise barriers are multifaceted;and 4) Exercise access and support are important. Participants reported that their cancer and cachexia had intensely altered their lives, including ability to exercise. Exercise was perceived as important and participants described a hope for exercise to improve their health and wellbeing. Yet, several complex exercise barriers, such as burdensome cancer symptoms and the overwhelming impact of the COVID-19 pandemic, hindered exercise participation and prevented participants from fully realizing the perceived benefits of exercise. Factors believed to improve exercise engagement and overcome exercise barriers included increased exercise support (e.g., professional supervision) and accessibility (e.g., convenient locations). Patient-reported exercise barriers and preferences can inform the design of exercise interventions, particularly within future research studies aiming to establish exercise feasibility and efficacy in people with advanced cancer and cachexia.

11.
BMC Palliat Care ; 21(1): 75, 2022 May 17.
Article in English | MEDLINE | ID: covidwho-1846827

ABSTRACT

Cachexia is a prevalent muscle wasting syndrome among people with advanced cancer that profoundly impacts patient quality of life (QoL) and physical function. Exercise can improve QoL, physical function, and overall health in people with cancer and may be an important addition to treatment approaches for cancer cachexia. Greater understanding of patients' perception of exercise can help elucidate the feasibility of implementing exercise interventions for cancer cachexia and facilitate the design of patient-centered interventions. We aimed to describe the perception of exercise in patients with advanced cancer and cachexia, and capture exercise motivators, barriers, and preferences, to inform the feasibility of exercise interventions. Individual interviews (n = 20) with patients with locally advanced or metastatic cancer with cachexia were conducted and analyzed using reflexive thematic analysis. Main themes from interviews were: 1) Life is disrupted by cancer and cachexia; 2) Exercise offers hope; 3) Exercise barriers are multifaceted; and 4) Exercise access and support are important. Participants reported that their cancer and cachexia had intensely altered their lives, including ability to exercise. Exercise was perceived as important and participants described a hope for exercise to improve their health and wellbeing. Yet, several complex exercise barriers, such as burdensome cancer symptoms and the overwhelming impact of the COVID-19 pandemic, hindered exercise participation and prevented participants from fully realizing the perceived benefits of exercise. Factors believed to improve exercise engagement and overcome exercise barriers included increased exercise support (e.g., professional supervision) and accessibility (e.g., convenient locations). Patient-reported exercise barriers and preferences can inform the design of exercise interventions, particularly within future research studies aiming to establish exercise feasibility and efficacy in people with advanced cancer and cachexia.


Subject(s)
COVID-19 , Neoplasms , Cachexia/therapy , Humans , Neoplasms/complications , Neoplasms/therapy , Pandemics , Quality of Life
12.
Indian Journal of Medical and Paediatric Oncology ; : 5, 2022.
Article in English | Web of Science | ID: covidwho-1799533

ABSTRACT

Megestrol acetate is one of the pharmacological agents used for cancer-associated fatigue. To date, there are no studies on its use in the treatment of post-COVID-19 (coronavirus disease 2019) fatigue. So, we report a case of metastatic carcinoma lung with a partial response with three cycles of palliative chemotherapy. He was contracted with mild COVID-19 infection post three cycles of his chemotherapy. Post this episode, fatigue was his main and most troublesome symptom. After a thorough clinical history, physical examination, and investigations, type 2 post-COVID-19 syndrome was diagnosed. After explaining the risks and benefits, we started the patient on low-dose megestrol acetate (160 mg/d per oral) with low to moderate benefits. However, upon increasing the dose to 480 mg/d, the benefit on the subjective quality of life was significant. Studies with a larger sample and randomized controlled trials have to be conducted to substantiate the hypothesis and actual effect of megestrol acetate in the treatment of post-COVID-19 fatigue.

13.
Journal of Crohn's and Colitis ; 16:i452, 2022.
Article in English | EMBASE | ID: covidwho-1722338

ABSTRACT

Background: Ozanimod, a sphingosine 1-phosphate (S1P) receptor S1P1 and S1P5 modulator, is approved in the United States for moderately to severely active ulcerative colitis (UC) and in multiple countries for relapsing multiple sclerosis (MS). We describe COVID-19 outcomes in ozanimod-treated UC or MS patients (pts) in active phase 3 openlabel extension (OLE) studies. Methods: A database search identified COVID-19 infection reports in ozanimod-treated pts with UC in the True North OLE and MS in the DAYBREAK OLE. The analysis period was November 1, 2019 to either August 31, 2021 (UC) or May 10, 2021 (MS). The last COVID-19 event from all pts with ≥1 event was analyzed. Results: Among 2792 ozanimod-treated pts with UC or MS, 258 developed COVID-19 (confirmed: 215);thus, the incidence in these clinical trial settings was 9.2% during the analysis periods. Most pts with confirmed cases (193/215 [89.8%]) had nonserious infections not requiring hospitalization or meeting other International Conference on Harmonisation criteria for a serious event. Of 611 ozanimod-treated pts with UC, 68 (11.1%) developed COVID-19 (confirmed: 55;Fig 1). A majority of UC pts with confirmed cases (45/55 [81.8%]) had nonserious COVID-19;most (54/55 [98.2%]) recovered (2 with sequalae) and 1 was recovering at data cutoff. One UC pt with confirmed COVID-19 discontinued ozanimod (1.8%), 23 temporarily interrupted it (41.8%), and 31 had no change to treatment (56.4%). No COVID-19-related deaths were reported in UC pts. Of 2181 ozanimod-treated pts with MS, 190 (8.7%) developed COVID-19 (confirmed: 160;Fig 2). Most MS pts with confirmed COVID-19 (148/160 [92.5%]) had nonserious cases;most (158/160 [98.8%]) recovered (5 with sequelae) (Fig 1). No MS pts with confirmed cases discontinued ozanimod, 61 temporarily interrupted it (38.1%), and 99 had no change to treatment (61.9%). Outcomes in 13 additional UC pts (Fig 1) and 30 additional MS pts (Fig 2) with suspected COVID-19 were similar to those with confirmed cases. There were 3 COVID-19-related deaths in the MS program. One pt died from a presumed pulmonary embolism;this pt had received high-dose corticosteroids for MS relapse immediately before COVID-19 symptom onset. Another pt died from suspected COVID-19-related respiratory failure. One tetraplegic, cachectic pt died from a lung abscess following COVID-19 infection. Conclusion: In the UC and MS OLE studies, most pts with confirmed COVID-19 had nonserious infections, recovered, and did not require ozanimod discontinuation. There were 3 deaths in MS patients (casefatality rate 1.6% in MS, 1.2% overall).

14.
JPEN J Parenter Enteral Nutr ; 45(S2): 41-46, 2021 11.
Article in English | MEDLINE | ID: covidwho-1718419

ABSTRACT

Advances in treatment of malignancy including novel pharmacologic therapies and surgical interventions has led to significant improvement in survival. As cancer becomes a chronic disease, nutrition interventions play an increasingly important role in short- and long-term outcomes. The current manuscript presents a case of a 66-year-old male with new diagnosis of pancreatic cancer diagnosed incidentally in the setting of COVID-19. Expert panelists in the field of nutrition discuss optimal strategies for diagnosis of malnutrition along with preoperative, perioperative, and postoperative optimization of nutrition. This discussion focuses on the use of probiotics, immune-modulating nutrition, fish oil, specialized proresolving mediators, and use of enteral and parenteral nutrition support.


Subject(s)
COVID-19 , Nutrition Disorders , Pancreatic Neoplasms , Aged , Humans , Nutrition Disorders/therapy , Pancreatic Neoplasms/complications , Pancreatic Neoplasms/diagnosis , Pancreatic Neoplasms/therapy , Parenteral Nutrition , SARS-CoV-2
15.
Clin Kidney J ; 15(2): 262-268, 2022 Feb.
Article in English | MEDLINE | ID: covidwho-1684567

ABSTRACT

BACKGROUND: Maintenance haemodialysis (MHD) patients have a high risk of initial mortality from coronavirus disease 2019 (COVID-19). However, long-term consequences of this disease in the MHD population are poorly described. We report the clinical presentation, outcome and long-term follow-up of MHD patients affected by COVID-19 in a multicentric cohort from the Paris, France area. METHODS: We conducted a retrospective analysis of clinical presentation and long-term follow-up of MHD patients affected by COVID-19 in 19 MHD centres in the Paris, France area. RESULTS: In this cohort of 248 patients with an initial mortality rate of 18%, age, comorbidities, dyspnoea and previous immunosuppressive treatment were associated with death at <30 days. Among the 203 surviving patients following the acute phase, long-term follow-up (median 180 days) was available for 189 (93%) patients. Major adverse events occurred in 30 (16%) patients during follow-up, including 12 deaths (6%) after a median of 78 days from onset of symptoms. Overall, cardiovascular events, infections and gastrointestinal bleeding were the main major adverse events. Post-COVID-19 cachexia was observed in 25/189 (13%) patients. Lower initial albuminaemia was significantly associated with this cachexia. No reinfection with severe acute respiratory syndrome coronavirus 2 was observed. CONCLUSIONS: This work demonstrates the long-term consequences of COVID-19 in MHD patients, highlighting both initial and long-term severity of the disease, including severe cachexia.

16.
Cells ; 11(3)2022 02 08.
Article in English | MEDLINE | ID: covidwho-1674519

ABSTRACT

Cancer cachexia remains a serious public health concern worldwide, particularly as cancer rates rise. Treatment is endangered, and survival is reduced, because this illness is commonly misdiagnosed and undertreated. Although weight loss is the most evident sign of cachexia, there are other early metabolic and inflammatory changes that occur before the most obvious symptoms appear. Cachexia-related inflammation is induced by a combination of factors, one of which is the release of inflammation-promoting chemicals by the tumor. Today, more scientists are beginning to believe that the development of SARS-CoV-2 (COVID-19) related cachexia is similar to cancer-related cachexia. It is worth noting that patients infected with COVID-19 have a significant inflammatory response and can develop cachexia. These correlations provide feasible reasons for the variance in the occurrence and severity of cachexia in human malignancies, therefore, specific therapeutic options for these individuals must be addressed based on disease types. In this review, we highlighted the role of key chemokines, cytokines, and clinical management in relation to cancer cachexia and its long-term impact on COVID-19 patients.


Subject(s)
COVID-19/metabolism , Cachexia/metabolism , Chemokines/metabolism , Cytokines/metabolism , Neoplasms/metabolism , COVID-19/epidemiology , COVID-19/virology , Cachexia/etiology , Humans , Inflammation/complications , Inflammation/metabolism , Inflammation Mediators/metabolism , Neoplasms/complications , Pandemics/prevention & control , SARS-CoV-2/physiology
17.
Italian Journal of Medicine ; 15(3):43, 2021.
Article in English | EMBASE | ID: covidwho-1567568

ABSTRACT

Background: In the CoViD-19 era any ground glass opacity is associated to SARS-CoV-2 pneumonia. Description of the case: A 33-year-old man is referred to the emergency department for cough and diarrhea. The patient's vital signs are notable for an oxygen saturation of 93% in RT. His heart rate and blood pressure are normal. He has cachexia, but the remainder of the physical examination findings were normal. A complete blood cell count reveals lymphopenia and anemia. A thoracic CT scan shows a bilateral ground glass opacity. Molecular swab for CoViD- 19 was positive with a high ct value. The patient is admitted to our Department for CoViD-19 pneumonia. He reports a long history of weight loss, weakness and diarrhea. His CRP, LDH and g-GT levels are elevated;remaining laboratory tests are all within normal limits. A peripheral blood smear shows rare schistocytes and activated lymphocytes. He is started to a large spectrum antibiotic therapy. The results of further workup for lymphopenia (HBV, HCV, HHV, Toxo, CMV and EBV, coprocolture, parasitological stool exam) are negative. The molecular swab for CoViD-19 is persistently negative as well as the serological test. A Candida albicans infection is found in the sputum colture. The HIV test results positive and a genotyping is detected. He starts with antiretroviral therapy and antifungal therapy with improvement of clinical status. Conclusions: The CT scan appearance in our patient was suggestive for SARS-CoV-2 infection, but the clinical history and laboratory findings directed our attention to different diagnosis and correct treatment.

18.
Nutrients ; 13(4)2021 Mar 29.
Article in English | MEDLINE | ID: covidwho-1159895

ABSTRACT

BACKGROUND: In older people with psychoneurological diseases, COVID-19 infection may be associated with a risk of developing or exacerbating dysphagia. The aim of the present study was to examine the relationship between eating/swallowing function and COVID-19 infection. METHODS: Subjects were 44 inpatients with confirmed COVID-19 infection being treated for schizophrenia in a psychiatric ward. Eating function was assessed using the Food Intake Level Scale (FILS) before and after infection. We also evaluated age, comorbidities, COVID-19 hospital stay, obesity index, weight loss rate, and chlorpromazine equivalent. RESULTS: Subjects had a mean age of 68.86 years. Pre-infection, 20 subjects had a FILS score of 7-9 (presence of eating/swallowing disorder) and 24 subjects had a score of 10 (normal). Eating function after infection resolution showed decreasing FILS score compared to that before infection in 14 subjects (74.14 years). Six subjects (79.3 years) transitioned from oral feeding to parenteral feeding. A ≥ 10% weight loss during infection treatment was significantly associated with decreased eating function and a transition to parenteral feeding. Chlorpromazine equivalents, comorbidities, and number of days of hospitalization showed no associations with decreased eating function. CONCLUSIONS: Preventing malnutrition during treatment for COVID-19 infection is important for improving post-infection life prognosis and maintaining quality of life (QOL).


Subject(s)
COVID-19/complications , Deglutition Disorders/etiology , Feeding and Eating Disorders/etiology , Schizophrenia/complications , Weight Loss , Aged , COVID-19/physiopathology , COVID-19/psychology , Deglutition Disorders/physiopathology , Deglutition Disorders/psychology , Eating/physiology , Eating/psychology , Feeding and Eating Disorders/physiopathology , Feeding and Eating Disorders/psychology , Female , Humans , Male , Middle Aged , Nutritional Status , Schizophrenia/virology
19.
Med Hypotheses ; 146: 110434, 2021 Jan.
Article in English | MEDLINE | ID: covidwho-1065479

ABSTRACT

Cancer cachexia (CC) is a progressive loss of muscle mass (with or without a decrease of adipose tissue). Gradual deterioration of the patient's fitness is resistant to nutritional intervention. The biochemical foundation of observed catabolism, detrimental protein, and energy balance is complex. However, the generalized inflammatory response plays a vital role. It is a kind of cytokine storm, which involves increased activity of TNF-α, IL-1, IL-6, and INF-γ. Pharmacological treatment of cachexia consists mainly of progestagens and glucocorticosteroids. Still, the assessment of new options limiting the harmful impact of cachexia could be beneficial. Chloroquine (CQ) and hydroxychloroquine (HCQ) are old antimalarial agents endowed with immunomodulatory properties. Being potent autophagy inhibitors, they could lead to a form of intracellular starvation in both cytokine-releasing cells and cancer cells, thus limiting the harmful impact of CC. CQ and HCQ are also efficient in particular connective tissue disorders. They have gained special attention since the World Health Organization announced the coronavirus disease 2019 (COVID-19) pandemic. According to initial reports, people with a severe inflammatory reaction showed significant benefits. Possibly they could not be attributed to the antiviral activity alone. It is worth noting that the cytokine storm in COVID-19, connective tissue disorders, and cancer cachexia share some similarities. Therefore, we hypothesize that low doses of CQ/HCQ may prove efficient in cancer cachexia.


Subject(s)
Cachexia/drug therapy , Cachexia/etiology , Chloroquine/therapeutic use , Hydroxychloroquine/therapeutic use , Models, Biological , Neoplasms/complications , Autophagy/drug effects , Autophagy/immunology , COVID-19/drug therapy , Cytokine Release Syndrome/drug therapy , Cytokine Release Syndrome/etiology , Cytokines/immunology , Humans , Immunologic Factors/therapeutic use , Pandemics , SARS-CoV-2
20.
Eur J Transl Myol ; 30(4): 9485, 2020 Dec 31.
Article in English | MEDLINE | ID: covidwho-1058556

ABSTRACT

In 2020, due to the COVID-19 pandemic, the annual meeting of the Interuniversity Institute of Myology (IIM), took place on a virtual platform. Attendees were scientists and clinicians, as well as pharmaceutical companies and patient organization representatives from Italy, several European countries, Canada and USA. Four internationally renowned Keynote speakers presented recent advances on muscle stem cells regulation, skeletal muscle regeneration, quantitative biology approaches, and metabolic regulation of muscle homeostasis. Novel, unpublished data by young trainees were presented as oral communications or posters, in five scientific sessions and two poster sessions. On October 15, 2020, selected young trainees participated to the High Training Course on "Advanced Myology", organized together with the University of Perugia, Italy. The course, on a virtual platform, showcased lectures on muscle development and regulation of muscle gene expression by international speakers, and roundtables discussions on "Single cell analysis of skeletal muscle" and "Skeletal muscle stem cell in healthy muscle and disease". The Young IIM Committee, composed by young trainee winners of awards in the past IIM Meeting editions, was directly involved in the selection of keynote speakers, the organization of scientific sessions and roundtables discussions tailored to the interests of their peers. A broad audience of Italian, European and North American participants contributed to the different initiatives. The meeting was characterized by a friendly and inclusive atmosphere, facilitating lively and stimulating discussions on emerging areas of muscle research. The meeting stimulated scientific cross-fertilization fostering novel ideas and scientific collaborations aimed at better understanding muscle normal physiology and the mechanisms underlaying muscle diseases, with the ultimate goal of developing better therapeutic strategies. The meeting was a success, and the number of meeting attendees was the highest of all IIM Meeting editions. Despite the current difficulties imposed by the COVID-19 pandemic, we are confident that the IIM community will continue to grow and deliver significant contributions to the understanding of muscle development and function, the pathogenesis of muscular diseases and the development of novel therapeutic approaches. Here, abstracts of the meeting illustrate the new results on basic, translational, and clinical research, confirming that our field is strong and healthy.

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