COVID Arm After Moderna Booster in Healthcare Worker: A Case Report.

SARS CoV-2 virus has infected more than 200 million people worldwide and more than 4.4 million in Indonesia. The vaccination program has become one of the solutions launched by many countries globally, including Indonesia, to reduce the transmission rate of COVID-19. Various vaccination platforms are produced, such as inactivated, viral vector, mRNA, and protein subunit. The vaccination booster program with mRNA platform (Moderna) was launched by the Indonesian government to give better protection for health care workers, particularly from delta variant. In this case report, we discuss one of the typical side effects of Moderna vaccine, which is referred to as the COVID arm.

Chemotherapy-Induced Intestinal Microbiota Dysbiosis Impairs Mucosal Homeostasis by Modulating Toll-like Receptor Signaling Pathways.

Chemotherapy-induced intestinal mucositis, a painful debilitating condition affecting up to 40-100% of patients undergoing chemotherapy, can reduce the patients' quality of life, add health care costs and even postpone cancer treatment. In recent years, the relationships between intestinal microbiota dysbiosis and mucositis have drawn much attention in mucositis research. Chemotherapy can shape intestinal microbiota, which, in turn, can aggravate the mucositis through toll-like receptor (TLR) signaling pathways, leading to an increased expression of inflammatory mediators and elevated epithelial cell apoptosis but decreased epithelial cell differentiation and mucosal regeneration. This review summarizes relevant studies related to the relationships of mucositis with chemotherapy regimens, microbiota, TLRs, inflammatory mediators, and intestinal homeostasis, aiming to explore how gut microbiota affects the pathogenesis of mucositis and provides potential new strategies for mucositis alleviation and treatment and development of new therapies.

Treatment-related adverse events of PD-1 and PD-L1 inhibitor-based combination therapies in clinical trials: a systematic review and meta-analysis.

BACKGROUND: Numerous ongoing trials are testing anti-PD-1-based or anti-PD-L1-based cancer treatment combinations. Understanding the toxicity profiles of treatment-related adverse events is essential. The aim of this study was to comprehensively investigate the incidences and profiles of treatment-related adverse events across different combination therapies. METHODS: We did a systematic review and meta-analysis comparing different chemotherapy, targeted therapy, immunotherapy, and radiotherapy combinations with PD-1 or PD-L1 inhibitors. We searched Pubmed, Embase, and Cochrane databases for articles published in English between Jan 1, 2000, and May 21, 2020, investigating globally approved PD-1 or PD-L1 inhibitor-based combination therapies. Only prospective trials reporting overall incidence or tabulated data of treatment-related adverse events were included. Trials investigating sequential therapies, comprising three or more classes of therapies, and enrolling less than ten patients were excluded. The primary outcomes were overall incidences and profiles for all-grade and grade 3 or higher treatment-related adverse events by random-effect models. Heterogeneity between studies was assessed with I2 statistics. The summary measures for main outcomes are incidences (95% CI). The 95% CI were calculated together with the incidence through a random-effects model with a logit transformation. The protocol is registered with PROSPERO (CRD42020189617). FINDINGS: We identified 2540 records, of which 161 studies (17 197 patients) met the inclusion criteria. The overall incidence of treatment-related adverse events in the chemotherapy combination was 97·7% (95% CI 96·4-98·5; I2=75%) for all-grade adverse events and 68·3% (60·7-75·0; I2=93%) for grade 3 or higher adverse events; in the targeted therapy combination was 94·5% (90·7-96·8; I2=86%) for all-grade adverse events and 47·3% (37·3-57·5; I2=93%) for grade 3 or higher adverse events; in the immunotherapy combination was 86·8% (80·9-91·1; I2=94%) for all-grade adverse events and 35·9% (29·5-42·9; I2=92%) for grade 3 or higher adverse events; and in the radiotherapy combination was 89·4% (69·0-96·9; I2=74%) for all-grade adverse events and 12·4% (4·4-30·6; I2=73%) for grade 3 or higher adverse events. For these four combination therapies, the most common all-grade adverse events were anaemia (45.4% [95% CI 32·4-59·1]), fatigue (34·3% [27·5-41·9]), fatigue (26·4% [19·2-35·2]), and dysphagia (30·0% [18·7-44·5]), respectively, and the most common grade 3 or higher adverse events were neutropenia (19·6% [13·5-27·7]), hypertension (9·3% [5·7-14·9]), lipase increased (7·2% [5·2-9·9]), and lymphopenia (10·3% [4·5-21·8]). All included randomised controlled trials had a low risk of bias. INTERPRETATION: Our study provides comprehensive data on treatment-related adverse events of different PD-1 or PD-L1 inhibitor-based combination therapies. Our results provide an essential reference of toxicity profiles of PD-1 or PD-L1 inhibitor-based combination therapies for clinicians in routine practice of cancer care. FUNDING: National Key Research and Development Programme, National Natural Science Foundation of China key program, National Natural Science Foundation of China general program, Chinese Academy of Medical Sciences Initiative for Innovative Medicine, Beijing Municipal Science and Technology Commission, Non-profit Central Research Institute Fund.

Iatrogenic male infertility: medical and surgical treatments that impair male fertility.

Many medical and surgical treatments result in impaired male fertility. Sometimes impairments are permanent, while other times they may be reversible. Clinicians who treat urologic and nonurologic problems, as well as those of us who treat male and female infertility should understand what treatments affect which aspects of reproduction and what options for management are available. Conditions for which treatment may impair fertility range from benign prostatic hyperplasia to cancer to behavioral health issues. This month's Views and Reviews summarizes these conditions, the mechanisms of fertility impairment as well as preemptive and posttreatment approaches for management.

Heart Rate Variability as a Non-invasive Objective Parameter for Predicting the Occurrence of Chemotherapy-induced Peripheral Neuropathy in Patients With Gastrointestinal Cancer.

BACKGROUND/AIM: Chemotherapy-induced peripheral neuropathy (CIPN) is one of the most common chemotoxicities. However, no effective clinical CIPN screening methods have been reported. This study aimed to investigate whether changes in heart rate variability (HRV) could predict the development of CIPN for early symptom control in chemotherapy-prescribed patients with gastrointestinal (GI) cancer. PATIENTS AND METHODS: Fifty-five GI cancer outpatients undergoing palliative chemotherapy including taxanes and/or platinum compounds were enrolled. CIPN was diagnosed using National Cancer Institute Common Toxicity Criteria for Adverse Event (NCI-CTCAE). HRV measures were derived from electrocardiogram signals. RESULTS: Twelve weeks after starting chemotherapy, 39 (70.9%) patients who complained of NCI-CTCAE grade 1-3 sensory changes were diagnosed with CIPN. Standard deviation of normal-to-normal R-R intervals (SDNN), high frequency (HF), low frequency (LF), and LF/HF ratio changed significantly during 3 assessment periods. Percentage changes in SDNN and HF were related to the occurrence of CIPN symptoms. A decision tree model indicated that patients with a rapid percentage change decrease in SDNN and HF were CIPN-positive. CONCLUSION: Using SDNN and HF, our decision tree predicted CIPN occurrence. The changes in HRV may occur earlier than sensory CIPN symptoms.

Evidence-based approaches for the management of side-effects of adjuvant endocrine therapy in patients with breast cancer.

The growing availability of more effective therapies has contributed to an increased survival of patients with breast cancer. In hormone receptor-positive early disease, increased survival is strongly correlated with the use of adjuvant endocrine therapy, but this therapy can cause side-effects that have major consequences in terms of treatment adherence and patients' quality of life. In premenopausal breast cancer survivors, these side-effects might be even more prominent due to the abrupt suppression of oestrogen associated with the most intense endocrine therapies. An important ambition of cancer care in the 21st century is to recover pre-cancer quality of life and emotional and social functions, which is only possible through the mitigation of the side-effects of anticancer treatments. This Review presents a comprehensive summary of the efficacy and safety data of the available interventions (hormonal and non-hormonal pharmacological strategies, non-pharmacological approaches, and complementary and alternative medicine) to control selected side-effects associated with adjuvant endocrine therapy (hot flashes, sexual dysfunction, weight gain, musculoskeletal symptoms, and fatigue), providing updated, evidence-based approaches for their management.

N-Acetylcysteine treatment of neonatal acetaminophen toxicity caused by transplacental transfer - a case report.

We describe a case of maternal acetaminophen toxicity leading to Caesarean section delivery of a pre-term neonate with acetaminophen-induced hepatic injury and encephalopathy at 33 weeks gestational age. Delayed treatment with N-acetylcysteine (NAC) was initiated in the baby 11 h after delivery, with eventual discharge of a healthy baby at 12 days of age. The baby was treated with a standard but extended duration NAC protocol. Post-operatively, liver biopsy of the mother demonstrated acetaminophen-induced hepatic injury overlying mild hepatic steatosis. This was also managed with NAC therapy leading to complete clinical resolution of acetaminophen induced hepatic injury and discharge on post-operative day 10. This case of delayed NAC therapy for the treatment of pre-term neonatal acetaminophen toxicity is one of very few reported in the literature and can be used as a guide in the management of subsequent cases.

The predictive value of body mass index on prognosis and adverse events of cancers treated with immunotherapy: a systematic review and meta-analysis.

OBJECTIVE: High body mass index (BMI) greater than 25 kg/m2 has a complex relationship with cancers. The aim of this systematic review and meta-analysis is to explore controversy over whether BMI is correlated with outcomes including survival and immunotherapy-related adverse events (irAEs) in cancer patients treated with immunotherapy. METHODS: We searched PubMed, Embase, Web of Science, and The Cochrane Library for relevant studies published up to June 2020. Title/abstract screening, full-text review, data extraction, and quality assessment were performed independently. Subgroup analysis was based on sex, treatment lines, the status of programmed death-ligand 1 (PD-L1), and tumor types. Sensitivity analysis was performed by synthesizing studies that adjusted for certain covariates or studies with good quality. Statistical heterogeneity was evaluated by the I2 value. Meta-analysis was performed with hazard ratio (HR) / odds ratio (OR) and 95% confidence intervals (CIs) as the effect measures. RESULTS: Twenty studies were included for survival and irAEs analyses. Patients with high BMI who underwent immunotherapy had longer overall survival (OS) (pooled hazard ratio, pHR = 0.71 [95% CI: 0.59-0.85]) and progression-free survival (PFS) (pHR = 0.76 [95% CI: 0.65-0.88]) than those with low BMI; at the same time, high-BMI patients had increased irAEs (OR = 2.54 [95% CI: 1.12-5.79]). CONCLUSION: In general, high BMI was correlated with improved OS and PFS in patients treated with immunotherapy along with a high risk of irAEs. However, discrepant findings from subgroup analyses urgently call for further analysis.

Toxicant effects on mammalian oocyte mitochondria†.

Oocyte mitochondria are unique organelles that establish a founder population in primordial germ cells (PGCs). As the oocyte matures in the postnatal mammalian ovary during folliculogenesis it increases exponentially in volume, and the oocyte mitochondria population proliferates to about 100 000 mitochondria per healthy, mature murine oocyte. The health of the mature oocyte and subsequent embryo is highly dependent on the oocyte mitochondria. Mitochondria are especially sensitive to toxic insults, as they are a major source of reactive oxygen species (ROS), they contain their own DNA (mtDNA) that is unprotected by histone proteins, they contain the electron transport chain that uses electron donors, including oxygen, to generate ATP, and they are important sensors for overall cellular stress. Here we review the effects that toxic insults including chemotherapeutics, toxic metals, plasticizers, pesticides, polycyclic aromatic hydrocarbons (PAHs), and ionizing radiation can have on oocyte mitochondria. This is very clearly a burgeoning field, as our understanding of oocyte mitochondria and metabolism is still relatively new, and we contend much more research is needed to understand the detrimental impacts of exposure to toxicants on oocyte mitochondria. Developing this field further can benefit our understanding of assisted reproductive technologies and the developmental origins of health and disease (DOHaD).

Efficacy of Aloe-Vera Use for Prevention of Chemotherapy-Induced Oral Mucositis in Children with Acute Lymphoblastic Leukemia: A Randomized Controlled Clinical Trial.

Oral mucositis can be caused by chemotherapy and can affect a patient's quality of life. Nowadays, to prevent chemotherapy-induced oral mucositis (CIOM) is a crucial point in palliative care centers. This trial aimed to assess the effectiveness of aloe-vera in that concept. The trial was accomplished at Hematology Department of Hospital of Children of Damascus University, Syria. Acute lymphoblastic leukemia (ALL) children were the population from which 26 children were enrolled in the study. They were aged between 3 and 6 years old and were randomly referred according to the intervention into two groups, Aloe-vera (AV) and sodium bicarbonate 5% (13 each). Spongeous sticks were used to help in applying the material on tongue, labial and buccal mucosa, lips, floor of the mouth, and hard palate. Two blinded external examiners evaluated oral mucosa weekly for up to 2 months using the World Health Organization grading scale. Mann-Whitney U test was used to analyze data. According to the observed findings, CIOM degrees were less severe in the aloe-vera group than in the sodium bicarbonate group. Statistically significant difference of occurrence of different CIOM degrees between groups was recorded in the 2nd, 3rd, 4th, and 7th weeks of follow-up period. Moreover, Mann-Whitney U test indicated that patients in the sodium bicarbonate group began CIOM sooner than those in the aloe-vera group with a statistically significant difference (p = .001). These findings show that topical application of aloe-vera solution is effective in the prevention of CIOM in ALL children.

Taste Function in Adults Undergoing Cancer Radiotherapy or Chemotherapy, and Implications for Nutrition Management: A Systematic Review.

BACKGROUND: Taste changes are commonly reported by people with cancer undergoing radio- or chemotherapy. Taste changes may compromise dietary intake and nutritional status. OBJECTIVE: To understand whether or not taste change is associated with cancer diagnosis or treatment modality in adults. METHODS: A systematic literature search up to December 31, 2019, was conducted using PubMed, Embase, and PsycInfo (International Prospective Register of Systematic Reviews protocol no. CRD42019134005). Studies in adults with cancer objectively assessing the effect of a cancer diagnosis or chemotherapy and/or radiotherapy treatment on taste function compared with healthy controls or within participant changes were included. Additional outcomes were food liking, appetite, dietary intake, nutritional status, and body composition. Reference lists of relevant articles were searched to identify additional articles. Quality was assessed using the Academy of Nutrition and Dietetics quality criteria checklist. RESULTS: A total of 24 articles were included, one of which consisted of two studies that reported the effects of radiotherapy and chemotherapy separately. From the total 25 studies reported in 24 published articles, 14 studies examined effects of radiotherapy, and remaining 11 studies examined chemotherapy. There is limited evidence of a cancer diagnosis per se contributing to taste dysfunction. Impaired taste function was reported in almost all radiotherapy studies, occurring as early as Week 3 of treatment and lasting for 3 to 24 months posttreatment. During chemotherapy, impairment of taste function was less consistently reported, occurring as early as the first few days of chemotherapy, and persisting up to 6 months posttreatment. Taxane-based chemotherapy was reported to affect taste function more than other treatments. Several studies reported reduced liking for food, appetite, and dietary intake. Only one study reported nutritional status of participants, finding no association between taste function and nutritional status. No studies examined associations between taste changes and body composition. CONCLUSIONS: This review highlights the importance of considering treatment modality in practice. Research is required to identify factors contributing to taste alteration and to inform evidence-based interventions.

Ocular Complications of Checkpoint Inhibitors and Immunotherapeutic Agents: A Case Series.

Background: Ophthalmologists have a role in assessing immune-related adverse events (IRAE) in oncology patients on immunotherapy. We assessed the utility of a hospital-wide toxicity team in referring patients with new ocular symptoms for examination. We also identified new immunotherapy agents causing ocular side-effects.Design: A cohort study of eight consecutive patients on immunotherapy, who developed ocular IRAE from November 1, 2017 to June 30, 2019. All were seen at the Ocular Immunology Division of the Wilmer Eye Institute and referred by the Johns Hopkins Toxicity Team.Results: All eight patients on had IRAEs; were treated with corticosteroid drops or observation with clinical resolution. Two new agents, epocadostat and daratumumab, were associated with the development of uveitis.Conclusion: Ophthalmologists play an important role in a hospital-wide toxicity team and need to include IRAEs in their differential diagnosis. Given new drug development, ophthalmologists may be the first to identify IRAEs.

Renal Repercussions of Medications.

Medications are a common cause of acute kidney injury and chronic kidney disease. Older patients with multiple comorbidities and polypharmacy are at increased risk and require extra diligence. Antimicrobials, antihypertensives, and nonsteroidal anti-inflammatory drugs are common offenders of drug-induced kidney injury. Other drug classes that can cause kidney damage include immunosuppressive medications, statins, proton pump inhibitors, and herbal supplements. Awareness of such medications and their mechanisms of nephrotoxicity helps decrease morbidity and mortality. If nephrotoxic agents cannot be avoided, hydration, avoiding concomitant nephrotoxic medications, and using the lowest effective dose for the shortest duration are strategies that can decrease risk of kidney damage.

Multimorbidity and Frailty: Tackling Complexity in Parkinson's Disease.

Parkinson's disease (PD) is a condition that predominantly affects older people. It is imperative that clinical management considers the other significant illnesses that people with PD accumulate as they age in conjunction with their resilience to cope with physiological change. Multimorbidity and frailty act synergistically to heighten the risk of adverse outcomes for older people with PD. These states are associated with increased likelihood of hospitalization, polypharmacy, adverse drug effects including the anticholinergic burden of medications, drug-disease and drug-drug interactions. Management should be integrated, holistic and individualised to meticulously balance the risks of interventions considering the vulnerability of the individual to recover from disturbance to their environmental, physical and cognitive equilibrium.

Management of cisplatin-associated toxicities in bladder cancer patients.

PURPOSE OF REVIEW: Cisplatin remains the treatment cornerstone for bladder cancer, either in neoadjuvant or in metastatic (cisplatin-gemcitabine or dose-dense methotrexate, vinblastine, and doxorubicin). Timely and adequate management of cisplatin's adverse events is important in order to avoid dose reductions, treatment delays, or cessation. Over the last years, several randomized studies and updated guidelines have been published on this subject. RECENT FINDINGS: The incidence, physiopathology, risk factors, preventive treatment, and optimal management of such complications will be presented, with special focus on cisplatin-associated nausea and vomiting, acute kidney injury (AKI), hypomagnesemia, neurotoxicity, and ototoxicity. SUMMARY: Optimal prevention of cisplatin-associated nausea and vomiting requires an aggressive approach with the use of a four-drug prophylactic regimen (NK1 receptor antagonist, 5-HT3 receptor antagonist, dexamethasone, olanzapine). The use of intensive hydration before and after cisplatin infusion has been the mainstay of AKI prevention. The management of hypomagnesemia and neurotoxicity remains largely symptomatic. In an adult population, no therapy has yet demonstrated benefits in the prevention or treatment of platinum-related ototoxicity.

Estimates of population-based incidence of malignant arrhythmias associated with medication use-a narrative review.

Certain medications are reported to be associated with acquired long-QT syndrome (ALQTS), which can degenerate into a potentially severe 'malignant' arrhythmia known as torsades de pointes (TdP). However, population-based estimations of the incidence of medication-associated malignant arrhythmia are limited. The purpose of this article is to review the clinical symptoms, cellular mechanism, categorization, and risk factors of these malignant arrhythmias, as well as illustrate results and methodological limitations of epidemiological literature which have previously estimated population-based incidence of ALQTS and malignant arrhythmia. Administrative databases in universal healthcare systems (such as Canada) can be used to provide a robust estimate of this incidence. We present a valid operational definition of medication-associated malignant arrhythmia, using Canadian hospital administrative data linked to prescription databases that can be used to estimate the population-based incidence. An estimation of incidence may have important implications with regard to understanding the potential widespread distribution of this adverse effect-which may influence medication prescribing patterns.

Effects of tyrosine kinase inhibitor therapy on skin toxicity and skin-related quality of life in patients with lung cancer: An observational study.

Epidermal growth factor receptor tyrosine kinase inhibitor (EGFR-TKI) therapy is the primary treatment option for patients with non-small cell lung cancer (NSCLC). However, one of the major adverse effects associated with this therapy is skin toxicity, which impacts the patient's quality of life. This study aimed to describe the severities and locations of skin toxicity, and to analyze their association with the quality of life in patients with advanced NSCLC who received EGFR-TKI therapy as first-line treatment.This cross-sectional and correlation study was conducted at a tertiary medical center in northern Taiwan between July 2015 and March 2016. Skin toxicity was assessed and graded using the National Cancer Institute Common Terminology Criteria for Adverse Events (version 4.03). The Skindex-16 scale was used to measure the skin disease-related quality of life.A total of 146 NSCLC patients who received EGFR-TKI therapy within the first 3 months of diagnosis were included in this study; 93.2% of these patients experienced skin toxicities. Approximately 70% of the patients developed xerosis and pruritus, while 50% had papulopustular eruptions and paronychia. The mean skin symptom impact score was 5.38 (standard deviation = 2.65). The skin-related quality of life varied widely among the participants but remained acceptable (mean score = 13.96, standard deviation = 16.55). Skin symptoms correlated significantly with poor quality of life (r = 0.50, P < .001). Younger patients and those treated with afatinib were the most affected, reporting the poorest quality of life. Patients who required EGFR-TKI dose reduction had experienced more severe skin symptoms than had patients who did not require it (7.35 vs 5.01, P < .001).Skin toxicity related to EGFR-TKI treatment impacts the quality of life in patients with NSCLC. During the treatment period, skin assessment and tailored management should be incorporated into the daily care plan.

Immune-related adverse events of checkpoint inhibitors.

Cancer immunotherapies have changed the landscape of cancer treatment during the past few decades. Among them, immune checkpoint inhibitors, which target PD-1, PD-L1 and CTLA-4, are increasingly used for certain cancers; however, this increased use has resulted in increased reports of immune-related adverse events (irAEs). These irAEs are unique and are different to those of traditional cancer therapies, and typically have a delayed onset and prolonged duration. IrAEs can involve any organ or system. These effects are frequently low grade and are treatable and reversible; however, some adverse effects can be severe and lead to permanent disorders. Management is primarily based on corticosteroids and other immunomodulatory agents, which should be prescribed carefully to reduce the potential of short-term and long-term complications. Thoughtful management of irAEs is important in optimizing quality of life and long-term outcomes.