Clinics and Practice

End-of-life decision making is a troublesome ethical dilemma. These decisions should be made in trustful patient–doctor relationships. We aimed to propose a balanced approach when discussing this complex issue. We categorized the research into four approaches and suggest that a multidisciplinary approach may be appropriate. We also analyzed the pitfalls of the multidisciplinary approach. Our conclusion is two-fold. First, discussions in this field should be based on real-world practice. If this is not the case, the proposal may be armchair theory, which is not effective in a clinical setting. Second, interdisciplinary researchers should not stick to their position too firmly and should listen to others. Otherwise, proposals made will be paternalistic or philosophically biased. Therefore, when philosophical collaboration is applied to the topic of clinical bioethics, it is necessary to thoroughly examine different positions and carry out careful discussions with consideration for medical care settings. Researchers must also understand what is needed for a trustful patient–doctor relationship. By making such efforts, clinical bioethics will contribute to the wellbeing of patients. Full article

This is a case report of a 5.6 cm glomangioma supplied by the femoral profunda artery in a 66-year-old male patient with severe peripheral artery disease. The patient complained of discomfort and mild pain at the place of the lesion and an accelerated growth rate in the last two months. A nodular mass located laterally on the left foot, elastic, covered with a thin skin, and mobile, was noted on the clinical exam. Doppler exam demonstrated an active vascular supply. CT angiography showed a femoral profunda artery blood supply and a severe asymptomatic bilateral peripheral artery disease (PAD). The lesion was removed entirely by surgery. A microscopy exam revealed a glomangioma. After surgery, the patient recovered unevenly. However, the patient experienced wound-healing issues that resolved after four weeks of surgery. Although the patient’s PAD was severe, the lesion presented with a burst in dimensions weeks before surgery. Full article

In 2014, the World Health Organization developed the End Tuberculosis Strategy with the goal of a 95% reduction in deaths from tuberculosis (TB) by 2035. The start of the COVID-19 pandemic and global lockdown has had a major impact on TB awareness, screening, diagnosis, and prompt initiation of treatment, inevitably leading to a significant setback. We explore pediatric tuberculosis through the lens of the COVID-19 era, investigating how COVID-19 has impacted pediatric TB cases in different regions of the world and what the implications are for management moving forward to mitigate these effects. Furthermore, in light of recent findings showing how exposed infants and children are at higher risk than we thought of contracting the disease, greater attention and resources are needed to prevent further downward trends. Full article

The influenza virus is associated with sickness, and in particular among vulnerable populations such as elderly and those with underlying disease with hospitalization and increased mortality rates. Vaccination is an effective way to prevent infection with influenza. However, undesirable side effects of the vaccination are commonly experienced, and comprise one of the primary reasons for a substantial group of individuals to refrain from vaccination. An effective treatment against vaccination side effects could increase the overall willingness to vaccinate against influenza. Here, four cases are presented that self-administered SJP-003 (a combination of 220 mg naproxen sodium, directly followed by a single oral dose of 60 mg fexofenadine HCL), 2 h before and 10 h after influenza vaccination. No flu-like symptoms and pain at the injection site were reported. These observations warrant further investigation of SJP-003 in double-blind, placebo-controlled clinical trials. Full article

(1) Background: To what extent is information manipulation by doctors acceptable? To answer this question, we conducted an exploratory study aimed at obtaining basic data on descriptive ethics for considering this issue. (2) Methods: A self-administered questionnaire survey was conducted on a large sample (n = 3305) of doctors. The participants were queried on (1) whether they consider that information manipulation is necessary (awareness), (2) whether they have actually manipulated information (actual state), and (3) their ethical tolerance. (3) Result: The response rate was 28.7%. Sixty percent of the doctors responded that information manipulation to avoid harm to patients is necessary (awareness), that they have actually manipulated information (actual state), and that information manipulation is ethically acceptable. (4) Conclusion: While the present survey was conducted among doctors in Japan, previous studies have reported similar findings in the United States and Europe. Based on our analysis, we hypothesize that a relationship of trust between patients and medical personnel is crucial and that information manipulation is not needed when such a relationship has been established. Full article

The prevalence of chronic daily headache (CDH) worldwide is 4–5%. Treatment for CDH with prophylaxis and abortive medications is often delayed, increasing disease severity. Consequently, increased usage of over-the-counter (OTC) analgesics can lead to medication overuse headache (MOH). This study aimed to assess factors affecting OTC analgesic overuse causing headaches. Methodology: A cross-sectional structured survey was conducted using voluntary response sampling. Among 1177 respondents, 459 individuals with headache were enrolled in the study. Results: Most participants were female (73.5%), almost half were aged 20–39 years (48.1%), and over half used OTC analgesics (56%). A significant association was found between OTC analgesic overuse and factors, such as chronic disease (p = 0.007), working status (p = 0.015), smoking (p = 0.02), headache frequency >15 days per month (p = 0.000), migraine-type headache (p = 0.01), preventive medicine use (p = 0.018), and emergency department visit (p = 0.018). Conclusion: OTC analgesic overuse among individuals with headache is affected by several factors, including the presence of chronic diseases, working status, smoking, and migraine-type headaches. However, preventive medicine and emergency department visits were considered to have protective effects. Health care providers should screen patients for MOH, increase their awareness, and follow MOH guidelines to treat chronic headache. Full article

Grade 4 adult gliomas are IDH-mutant astrocytomas and IDH-wildtype glioblastomas. They have a very high mortality rate, with survival at 5 years not exceeding 5%. We aimed to conduct a clinical imaging and morphogenetic characterization of them, as well as to identify the main negative prognostic factors that give them such aggressiveness. We conducted a ten-year retrospective study. We followed the clinical, imaging, and morphogenetic aspects of the cases. We analyzed immunohistochemical markers (IDH1, Ki-67, and nestin) and FISH tests based on the CDKN2A gene. The obtained results were analyzed using SPSS Statistics with the appropriate parameters. The clinical aspects representing negative prognostic factors were represented by patients’ comorbidities: hypertension (HR = 1.776) and diabetes mellitus/hyperglycemia (HR = 2.159). The lesions were mostly supratentorial, and the temporal lobe was the most affected. The mean volume was 88.05 cm³ and produced a midline shift with an average of 8.52 mm. Subtotal surgical resection was a negative prognostic factor (HR = 1.877). The proliferative index did not influence survival rate, whereas CDKN2A gene mutations were shown to have a major impact on survival. We identified the main negative prognostic factors that support the aggressiveness of grade 4 gliomas: patient comorbidities, type of surgical resection, degree of cell differentiation, and CDKN2A gene mutations. Full article

Progress in the management of rare diseases, including rare cancers, is dependent upon clinical trials; however, as many as 32% of rare-disease trials go uncompleted or unpublished due to insufficient accrual. Monitoring practices may differ between institutions. We sought to survey the regulatory standards for various trial types among major U.S. cancer centers. A 10-question survey was designed using Qualtrics assessment software. The survey was sent via email to an internal server of member institutions of the Association of American Cancer Institutes (AACI). Of 103 AACI centers, 31% completed the survey (n = 32). Respondents differed in their definitions of a rare disease, minimum expectations for rare tumor studies, and frequency of accrual monitoring by their institutional Protocol Review and Monitoring Committee. Seventy-three percent of respondents did not close trials based on low accrual. Strategies to optimize accrual included investigator incentives for high accrual and penalties for low accrual in 37% and 13% of respondents, respectively. Full article

Bioprosthetic valve thrombosis (BPVT) is considered a relatively rare but life-threatening clinical entity. Thus, there is the need of high clinical suspicion in order to make a timely diagnosis and related appropriate therapeutic interventions. In this regard, the management of BPVT is high risk, whatever the option taken (surgery and/or systemic fibrinolysis). The presence of severe comorbidities—as decompensated cirrhosis—further complicates the clinical decision-making process, calling for a patient-tailored integrated multidisciplinary approach. We report a challenging case of a 45-year-old patient with mitral bioprosthetic valve thrombosis and hepatitis C virus (HCV)-related cirrhosis complicated by active duodenal variceal bleeding. Full article

A 13-year-old girl with Jervell and Lange-Nielsen syndrome associated congenital long QT syndrome (LQTS) and central deafness was admitted for generalized seizures. LQTS had been diagnosed after birth and confirmed at genetic testing. β-blocker treatment was immediately started. Despite this, since the age of 12 months, recurrent cerebral seizures occurred leading to the diagnosis of epilepsy. Anti-convulsive therapy was initiated but without success. At the last admission, nadolol dosage seemed infratherapeutic. Considering malignant ventricular arrhythmias as the cause of seizures, the β-blocker dosage was adjusted to weight and levels of magnesium and potassium optimized. Furthermore, the patient received an implantable Medtronic Reveal LINQ Recorder^®. Since then, the adolescent has been asymptomatic with no arrhythmia documented. LQTS is due to one or more mutations of genes coding for ion channels. It may induce malignant ventricular arrhythmias and is a major cause of sudden cardiac death in children. Generalized cerebral seizures are extra-cardiac manifestations caused by decreased cerebral perfusion during ventricular arrhythmia. They are commonly misinterpreted as manifestations of epilepsy. For any patient with known or unknown LQTS who presents seizures with resistance to anti-convulsive therapy, a cardiac electrophysiological investigation should be performed promptly to ensure etiological diagnosis and optimize treatment. Full article

Adenocarcinoma of the small bowel is rather uncommon and several etio-pathogenic factors have been proposed. We report a case of multiple synchronous adenocarcinomas arising in the non-ampullary duodenum and first tract of the jejunum in a background of Brunner’s glands agenesia, chronic duodenitis, and extensive dysplasia in a 64 year-old woman. To the best of our knowledge such association has not been reported so far. Full article

Programmed death-ligand (PD-L) 1 and 2 are ligands of programmed cell death 1 (PD-1) receptor. They are members of the B7/CD28 ligand-receptor family and the most investigated inhibitory immune checkpoints at present. PD-L1 is the main effector in PD-1-reliant immunosuppression, as the PD-1/PD-L pathway is a key regulator for T-cell activation. Activation of T-cells warrants the upregulation of PD-1 and production of cytokines which also upregulate PD-L1 expression, creating a positive feedback mechanism that has an important role in the prevention of tissue destruction and development of autoimmunity. In the context of inadequate immune response, the prolonged antigen stimulation leads to chronic PD-1 upregulation and T-cell exhaustion. In lung cancer patients, PD-L1 expression levels have been of special interest since patients with non-small cell lung cancer (NSCLC) demonstrate higher levels of expression and tend to respond more favorably to the evolving PD-1 and PD-L1 inhibitors. The Food and Drug Administration (FDA) has approved the PD-1 inhibitor, pembrolizumab, alone as front-line single-agent therapy instead of chemotherapy in patients with NSCLC and PD-L1 ≥1% expression and chemoimmunotherapy regimens are available for lower stage disease. The National Comprehensive Cancer Network (NCCN) guidelines also delineate treatment by low and high expression of PD-L1 in NSCLC. Thus, studying PD-L1 overexpression levels in the different histological subtypes of lung cancer can affect our approach to treating these patients. There is an evolving role of immunotherapy in the other sub-types of lung cancer, especially small cell lung cancer (SCLC). In addition, within the NSCLC category, squamous cell carcinomas and non-G12C KRAS mutant NSCLC have no specific targetable therapies to date. Therefore, assessment of the PD-L1 expression level among these subtypes of lung cancer is required, since lung cancer is one of the few malignances wherein PD-L1 expression levels is so crucial in determining the role of immunotherapy. In this study, we compared PD-L1 expression in lung cancer according to the histological subtype of the tumor. Full article

Background: Tele-prehabilitation is a behaviour change intervention that facilities the modification of unhealthy lifestyle behaviours. Understanding patients’ experiences of tele-prehabilitation provides important insights into service improvement. In this study, we aimed to describe our patients’ perceptions of tele-prehabilitation and capture their capabilities, opportunities, and motivations to participate. This was a qualitative study to inform our service design and delivery. Methods: Following purposive sampling, 22 qualitative semistructured interviews were conducted with patients in the community that had completed tele-prehabilitation. Interviews were recorded and transcribed. Deductive content analysis was used to map the identified themes against theoretical determinants of health behaviour change. Results: We conducted 22 interviews. Our patients described their overall experience of tele-prehabilitation as positive and provided important insights that impacted their capabilities, opportunities, and motivations to engage with our service. Our team provided them the capabilities and self-efficacy to engage by personalising multimodal plans and setting goals. The remote delivery of our service was a recurring positive theme in providing flexibility and widening accessibility to participation. A missed opportunity was the potential for peer support through shared experiences with other patients. Patients showed greater motivation to participate for immediate perioperative benefit compared to long-term health gains. Conclusion: Patients’ experiences and perspectives of tele-prehabilitation can be enhanced by incorporating the findings from this qualitative study into service redesign and delivery. We recommend: (1) applying holistic principles in care and goal-setting, (2) delivering a combination of home-based and in-centre programmes, and (3) engaging with patients at the start of their cancer journey when they are most motivated. In turn, this can result in more effective uptake, improve adherence to interventions, and greater satisfaction. Full article

Background: Cryptoglandular anal fistulae can significantly affect patient quality of life (QoL), making it essential to ensure that any study of fistula treatment assesses the impact on QoL. The aim of this systematic review was to evaluate the content validity of Patient-Reported Outcome Measures (PROMs) that assess QoL in patients with a fistula. Methods: MEDLINE, EMBASE, PsycINFO, and Scopus were searched and studies assessing the content validity of patient-reported QoL measurement instruments, or PROM development studies in patients with cryptoglandular anal fistulae, were included. Data were extracted from eligible studies to determine the instruments’ relevance, comprehensiveness, and comprehensibility, and their quality was assessed according to COnsensus-based Standards for the Selection of health Measurement Instruments (COSMIN). Results: Two PROM development studies were identified, both of which described the development of a disease-specific QoL measurement instrument for patients with cryptoglandular anal fistulae. The overall content validity of these instruments was inconsistent and supported by very low-quality evidence. There were no studies assessing the content validity of established QoL measurement instruments in patients with fistulae. Conclusions: This systematic review could not establish the content validity of the available QoL PROMs for patients with anal fistulae, due either to the absence of designated content validity studies or a lack of comprehensiveness of the available PROMs. This highlights an important gap in the literature that needs to be addressed to ensure high-quality outcome assessment in patients with fistulae. Full article

(1) Purpose: In 2020, wearing of face masks was mandated in the United States in an effort to lessen transmission of the novel 2019 coronavirus disease (COVID-19) pandemic; however, long-term mask wearing may present with unintended side-effects in both ophthalmic and otolaryngologic clinical practice. This study aims to examine if mask wearing increased the incidence of primarily chalazion, blepharoconjunctivitis, and rhinitis occurrence during the mask-mandated COVID-19 pandemic period. (2) Methods: Medical records from tertiary academic center clinics were analyzed for incidence of ophthalmic and otolaryngologic diagnoses of interest (blepharoconjunctivitis- and rhinitis-related disorders). Data were collected from a pre-pandemic (March 2019–February 2020) and a mid-pandemic window (March 2020–February 2021) during which widespread mask mandates were implemented in Texas. Comparison was performed using a t-test analysis between incidence of chosen diagnoses during the described time periods. (3) Results: Incidence of ophthalmic disorders (primarily blepharoconjunctivitis and chalazion) in the pre-pandemic versus mid-pandemic windows did show a significant difference (p-value of 0.048). Similarly, comparison of otolaryngologic diagnoses (primarily rhinitis and related conditions) between the two time periods showed a significant difference (p-value of 0.044) as well. (4) Conclusion: Incidence of the chosen ophthalmic and otolaryngologic disorders did increase during periods of mask mandates. While these findings are preliminary, further studies are warranted to understand other factors that may have played a role in eye and nose pathology. Full article

Non-specific chronic low back pain (NSCLBP) is defined as a complex disorder involving structural, biomechanical, cognitive, psychological, social, and lifestyle factors. Non-pharmacological approaches such as exercise and physical therapy have been proposed in first-line treatments, along with psychological follow-up and pain medication if needed. Our objective was to evaluate the effectiveness of an intensive rehabilitation program with HUBER (a multi-axis motorized platform equipped with force sensors, allowing patients to perform physical exercises in an isometric mode) on the spine flexion-to-extension ratio at 60 and 120°/s, pain, and trunk flexibility in individuals with NSCLBP. Twelve participants underwent a clinical evaluation including isokinetic spine strength and participated in a 6-week rehabilitation program with HUBER 360 Evolution. The main findings of this pilot study show that the flexor/extensor ratios at 60°, the flexibility of the hamstring and quadriceps, and muscular endurance of the trunk, disability, and quality of life were significantly improved at the end of the rehabilitation program (p < 0.05). Low back pain and analgesic medication were also reduced. Exercising with the HUBER Platform seems to be effective in managing NSCLBP but a randomized study with a larger sample size and a control group is necessary. Full article

During the last couple of critical years, worldwide, there have been more than 550 million confirmed cases of COVID-19, including more than 6 million deaths (reported by the WHO); with respect to these cases, several vaccines, mainly mRNA vaccines, seem to prevent and protect from SARS-CoV-2 infection. We hypothesize that oxidative stress is one of the key factors playing an important role in both the generation and development of various kinds of disease, as well as antibody generation, as many biological paths can generate reactive oxygen species (ROS), and cellular activities can be modulated when ROS/antioxidant balance is interrupted. A pilot study was conducted in two stages during the COVID-19 pandemic in 2021 involving 222 participants between the ages of 26 and 66 years. ROS levels were measured before an after vaccination in the blood samples of 20 individuals who were vaccinated with two doses of mRNA vaccine, and an increase in ROS levels was observed after the first dose, with no modifications observed until the day before the second vaccination dose. A statistically significant difference (p < 0.001) was observed between time points 3 and 4 (before and after second dose), when participants were vaccinated for the second time, and ROS levels decreased from 21,758 to 17,580 a.u. In the second stage, blood was collected from 28 participants 45 days after COVID-19 infection (Group A), from 131 participants 45 days after receiving two doses of mRNA vaccine against COVID-19 (Group B), and from 13 healthy individuals as a control group (Group C). Additionally, antibodies levels were measured in all groups to investigate a possible correlation with ROS levels. A strong negative correlation was found between free radicals and disease antibodies in Group A (r = −0.45, p = 0.001), especially in the male subgroup (r = −0.88, p = 0.001), as well as in the female subgroup (r = −0.24, p < 0.001). Furthermore, no significant correlation (only a negative trend) was found with antibodies derived from vaccination in Group B (r = −0.01), and a negative trend was observed in the female subgroup, whereas a positive trend was observed in the male subgroup. Full article

Introduction: Rheumatoid arthritis (RA) is a common autoimmune illness that manifests mostly as chronic, symmetric, and progressive polyarthritis with a global frequency of 0.3–1.0%. RA is a disease that affects people all over the world. In India, the prevalence is estimated to be 0.7%, with around 10 million persons suffering from RA. Most people with rheumatoid arthritis experience fatigue on most days, with over 70% experiencing symptoms similar to chronic fatigue syndrome. Patients rate fatigue as a top priority and believe this unmanageable symptom is ignored by clinicians; a systematic review shows the biological agents for RA inflammation have only a small effect on fatigue. Fatigue predicts and reduces the quality of life, and it is as difficult to cope with as pain. Physicians have traditionally concentrated on the inflammatory aspects of the illness (e.g., synovitis), whereas RA patients have prioritized pain, exhaustion, sleep difficulties, and other quality-of-life issues. Aims and Objectives: The basic aim of the study was to access the incidence of fatigue in rheumatoid arthritis and evaluate its impact on the quality of life in these patients using the MAF scale (multidimensional assessment of fatigue) after prior permission for the first time in an Asian population. Results: A total of 140 subjects and 100 controls were included in the study. Age was closely matched between the study subjects and controls. Among study subjects with the disease, 94 (67%) had a disease duration ≤ 5 years, 26 (19%) had a disease duration between 6–10 years, 10 (7%) had a duration of 11–15 years and 10 (7%) had >10 years disease duration. Among the sample, 31 (25%) study subjects had a DAS score ≤ 4.0, 63 (50%) study subjects had a DAS score (disease activity score) between 4.01 and 6.0, and in the remaining 31 (25%) study subjects, the DAS score was >6.0. The mean DAS score among study subjects was 4.96, and the study subjects had a mean activity of daily living (ADL) score of 11.64; controls had a mean score of 2.42 with a statistically significant p-value. The global fatigue index was higher in study subjects, with a mean of 33.16 in contrast with a mean of 14.41 in the controls with a significant p-value. Conclusion: Our study fatigue was a persistent problem, despite treatment. The median level of fatigue experienced by study subjects with RA was high. Therefore, as persistent fatigue is associated with functional loss, fatigue in RA remains an ‘unmet need’ and continues to be ignored by clinicians. Full article

It is an acknowledged fact that SARS-CoV-2 exhibits tropism for the human placenta. A possible mechanism of SARS-CoV-2 entry into host cells is via angiotensin-converting enzyme 2 (ACE2) receptors, which are expressed in trophoblasts, endothelial cells, and macrophages. The present study describes a case of spontaneous miscarriage in the 20th gestational week after maternal SARS-CoV-2 infection. The placenta and various fetal organs were examined for structural alterations and expression of the viral nucleocapsid protein and several immune cell markers via immunohistochemistry (IHC). Histopathological examination of the placenta revealed acute chorioamnionitis, acute subamnionic placentitis, multiple intervillous thrombi, increased fibrinoid deposition, and necrotic changes of the chorionic villi. Immunohistochemistry confirmed the presence of SARS-CoV-2 nucleocapsid protein regions predominantly in the syncytiotrophoblast. Staining of the placental tissue for different markers helped elucidate the distribution of immune cells. Pathomorphological examination of the fetal organs demonstrated changes in microcirculation with the presence of sludge phenomenon and diapedesis haemorrhages, mostly in the lungs, brain, and myocardium. IHC staining of fetal organs revealed expression of SARS-CoV-2 nucleocapsid protein, which was detected to the highest extent in the brain, lungs, and liver. The findings of the present report support the hypothesis of possible vertical transmission of SARS-CoV-2 from mother to fetus. Full article