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The etiology of acute hepatic cytolysis is complex, and a thorough laboratory investigation is needed to find the causative agent and guide the clinician toward a specific treatment. Viral hepatitis A is a well-known cause of acute hepatitis, but other viruses and bacteria can lead to or contribute to liver damage. We report the case of a young male patient with triple infection with hepatitis A virus, Epstein–Barr virus, and Leptospira spp. To our knowledge, this is the first case of an HAV, EBV, and Leptospira triple infection, and it aims to bring awareness about the possibility of double or triple infection with such pathogens that are highly cytotoxic for the liver tissue since all three pathogens are known to cause or contribute to the onset of acute hepatitis. It was deduced that the source of the infection likely happened during a two-week visit to the countryside in Romania, returning 16 days before the onset of symptoms. The evolution was favorable receiving treatment with amoxicillin/clavulanic acid (1200 mg/8 h); glucose 5% 500 mL/day; 0.9% saline 500 mL/day; phenobarbital 1 tablet/day (200 mg); vitamins B1 and B6 and a complex of vitamin C and D3 and zinc. Lactulose syrup was also administered when the patient had no bowel movement for more than 24 h to prevent the onset of hepatic encephalopathy, and the patient was discharged after 20 days. This case suggests that a detailed anamnesis can raise suspicion about more uncommon causes of hepatic cytolysis and lead to a broader and more complex laboratory investigation, thus improving the quality of patient care. Yet, this is the only case previously reported to compare different management options and patient outcomes. [ABSTRACT FROM AUTHOR]

Ancient and modern doctors often take “warmth of labor” as an important rule for the treatment of asthenia, but their understanding is different, the solution of “warming” is especially controversial. On the basis of tracing the source of words, combined with medical theory and clinical thinking, we searched the relevant records of labor syndrome in ancient books and documents and further examined the connotation of “warmth of labor”, the meaning of “warming” should cover three aspects: warming is nourishing, focusing on the restoration of genuine qi; warming is softness, paying attention to the relaxation of governance; and warming is the meaning of transformation, focusing on the cultivation of vitality. These three aspects are in fact one. They all aim at cultivating, transforming, and generating the essence of life, which can be used for reference. [ABSTRACT FROM AUTHOR]

Background Palbociclib has gained a central role in the treatment of hormone receptor-positive (HR+)/human epidermal growth factor receptor 2-negative (HER2−) advanced breast cancer (ABC). Despite its manageable toxicity profile, venous thromboembolism (VTE) or interstitial lung disease (ILD)/pneumonitis may infrequently occur. Therefore, we provide a comprehensive summary of the safety and tolerability of the combination of endocrine therapy and palbociclib among patients included in the randomized phase 2 PARSIFAL study. Materials and Methods Patients with endocrine-sensitive HR+/HER2- ABC and no prior therapy in an advanced setting (n  = 486) were randomly assigned 1:1 to receive fulvestrant–palbociclib (FP) or letrozole–palbociclib (LP). Laboratory tests and the incidence of adverse events (AEs) were recorded at baseline and day 1 of each cycle. Progression-free survival (PFS) was estimated for patients with and without VTE. Results A total of 483 patients were analyzed. Neutropenia, leukopenia, anemia, asthenia, arthralgia, fatigue, and diarrhea were the most frequent AEs in both groups. Febrile neutropenia occurred in 3 (1.2%) patients of the FP group and in 1 (0.4%) patient in the LP group. Six (2.5%; 0.4% grade 3) patients in the FP group and 6 patients (2.5%; 0.4% grade 3) in the LP group experienced ILD/pneumonitis. Pulmonary embolism was reported in 12 (5.0%) patients in the FP group and 6 (2.5%) patients in the LP group. Advanced age at baseline was the only factor significantly associated with an increased risk of pulmonary embolism (P  < .01). Conclusion The PARSIFAL data confirmed the favorable safety profile of both palbociclib regimens. VTE and ILD/pneumonitis were occasionally reported, and their early detection allowed patients to continue treatment effectively without detriment to efficacy. ClinicalTrials.gov Identifier NCT02491983; https://clinicaltrials.gov/ct2/show/NCT02491983). [ABSTRACT FROM AUTHOR]

Splenosis is a heterotopic autotransplantation of splenic tissue after rupture of the splenic capsule caused by injury or during elective splenectomy in the management of haematological diseases. Splenosis might cause nonspecific abdominal symptoms but is usually asymptomatic, and it is diagnosed accidentally as an abdominal tumour. It is rarely diagnosed in the paediatric population. We describe a 12-year-old female patient with hereditary spherocytosis admitted to the hospital 3 years after elective splenectomy and cholecystectomy. In medical imaging abdominal and pelvic tumours together with enlarged lymph nodes were found. During laparoscopic surgery many nodules were found with morphology similar to splenic tissue in the omentum, on the surface of small intestine, colon and peritoneum. Results of histopathological examination confirmed splenosis. Splenosis should be considered in differential diagnosis of abdominal tumours in paediatric patients with a history of elective splenectomy or spleen injury. [ABSTRACT FROM AUTHOR]

In recent years, the concept of debility has gained a lot of attention. In critical theory and in the critical medical humanities, the concept has come to refer specifically to the general ill-health of ordinary lives under neoliberal capitalism; as such, it has triggered a surge of interest in large-scale affective assemblages that incapacitate multitudes of bodies. This article proposes neoliberal misfit as a conceptual tool to remedy the dissolution of subjectivity in these discussions. Pushing back against Jasbir Puar specifically, it argues that processes of debilitation produce a particular type of subject formation often ignored in this body of work. The article does so by distinguishing this subject formation in three contemporary illness narratives that dramatize encounters between ill bodies and accelerating rhythms, competitive atmospheres, and mobile attachments, respectively. Ultimately, the aim is to help the critical medical humanities capture how neoliberal environments affect the self-perception of people suffering from ill-health. [ABSTRACT FROM AUTHOR]

An 80‐year‐old woman received a dual chamber pacemaker (Boston Scientific Accolade MRI DR) for pre‐syncopal episodes associated with transient II‐degree atrioventricular block type 1 and 2:1, recorded in 24‐h Holter monitoring. Due to residual AV conduction with I‐degree AV block, the pacemaker was set with the RYTHMIQ® algorithm, in order to reduce inappropriate ventricular pacing. A month later the patient started to complain of severe asthenia and bradycardia (46‐48 bpm). Telemetry‐supported pacemaker control revealed III‐degree AV block with junctional escape rhythm, unmasking missed switch of RYTHMIQ® algorithm. [ABSTRACT FROM AUTHOR]

Asthenia syndrome is an actual problem during the pandemic of a new coronavirus infection (COVID-19) due to the high frequency of occurrence, regardless of the severity of the disease, this condition can develop in all patients who have had COVID-19. The clinical picture of postcovid syndrome is very diverse, but the most common are asthenic disorders, anxiety-depressive disorders and cognitive disorders.

Introduction. Asthenia is an urgent problem during the pandemic of new coronavirus infection (COVID-19) because of its high frequency regardless of the severity of the disease.The purpose of this subanalysis of data from the multicenter controlled randomized clinical trial TONUS was to evaluate the efficacy and safety of meldonium therapy for аsthenia in COVID-19 survivors.Materials and methods. A total of 880 patients with asthenia who underwent COVID-19 within the last 6 months were included in the analysis. The efficacy of asthenia therapy was assessed by the MFI-20 scale, Schulte tables, and the General Clinical Impression (CGI) scale. All patients were previously randomized in two parallel branches of the TONUS study, including patients without concomitant disease in TONUS-1 (who received meldonium 500 mg/day for 14 days in the main group) and patients with cardiovascular or cerebrovascular disease in TONUS-2, who received meldonium at a dose of 1000 mg/day for 42 days in the main group. In both arms of the study, the drugs in the comparison groups were multivitamin complexes.Results. For the TONUS-1 groups.In the group of patients receiving meldonium compared with the control group (p < 0.001): total MFI-20 score decreased and was 31 (25; 40); MFI-20 –35 (–46; 23); performance value –5 (–11; –2) seconds; proportion of patients with significant improvement (by CGI-I) by the end of follow-up was 92.8%. For TONUS-2 groups.In the group of patients receiving meldonium compared with the control group (p < 0.001): total MFI-20 score decreased to 35 (27; 44); MFI-20 –34 (–46; –21), performance value –5 (–11; –2), proportion of patients with significant improvement (by CGI-I) by end of follow-up – 90.8%.Conclusion. Significant positive dynamics and regression of asthenia were noted in the groups of patients receiving meldonium in comparison with the control groups.

Introduction. Asthenia, vegetative manifestations, sleep disturbances and psycho-emotional background are companions of the coronavirus infection, the issue of drug correction of which is especially relevant. These symptoms disrupt the habitual way of life of patients for a long time, and in special cases lead to disability.Aim. To study the mental, somatoform and cognitive aspects of anxiety disorders after coronavirus infection during treatment with tofisopam (Grandaxin®) 150 mg/day.Materials and methods. The study included patients who had experienced a new coronavirus infection, who, after the end of treatment for the underlying disease, had complaints suggesting the presence of an anxiety disorder. The Hamilton scale was used to assess the level of anxiety. Examination of patients was carried out before the start of treatment, after 2, 4 and 6 weeks of therapy.Results and discussion. Prior to the start of therapy, all patients had an overall high level of anxiety: the average HAM-A score was 31.4 ± 2.92 points. At the end of Grandaxin® therapy, all patients showed a decrease in the level of anxiety: the average HAM-A score was 12.08 ± 2.27 points (p < 0.001). The maximum decrease in the severity of vegetative disorders was noted by the end of the 6th week of therapy with Grandaxin®. Thus, the indicator of this subscale decreased by more than 2 times – from 2.46 ± 0.54 to 1.05 ± 0.28 points (p < 0.001). The severity of insomnia during six weeks of therapy with Grandaxin® decreased from 2.56 ± 0.54 to 0.96 ± 0.45 points (p < 0.001).Conclusion. Psycho-emotional disorders (more often in the form of increased personal anxiety), sleep disorders, vegetative disorders, asthenic syndrome significantly affect the quality of life of patients who have had a new coronavirus infection. Involvement of the structures of the autonomic nervous system and central structures that regulate GABAergic transmission leads to significant vegetative failures, which requires pathogenetically substantiated drug correction of these disorders.

The study aimed to describe the outcomes of the voice use reduction (VUR) program on voice quality and vocal fatigue (VF) in occupational voice users (OVUs). A within-subject, quasi-experimental, pre-test, post-test research design was performed on 30 OVUs. Perceptual and acoustic outcome measures were employed pre-and post-implementation of the VUR, including the GRBASI 4-point rating scale, jitter, shimmer, fundamental frequency (F0), harmonic-to-noise ratio (HNR), maximum phonation time (MPT), frequency min and max, intensity min and max, the dysphonia severity index (DSI), and the vocal fatigue index (VFI). The pre-and post-test outcomes revealed significant (p < .001) decreases in perceptual G (Grade of hoarseness), R (Roughness), A (Asthenia), S (Strain), and I (Instability). Perceptual normality in these areas increased significantly (p < .001). Acoustic measures revealed significant (p < .05) decreases in Jitter%, Intensity (dB) Min, and DSI scores as well as significant (p < .05) increases in MPT /a/, /s/, and /z/, Frequency (Hz) Max, and F0 (Hz) Max, indicating improved voice quality at post-test. The VUR program positively affected and improved OVUs’ perception of VF in the areas of tiredness of voice and physical discomfort. OVUs strongly perceive improvement of VF symptoms with rest regardless of the current level of VF they are experiencing. When approaching OVUs, clinicians are encouraged to use a combination of direct voice therapy and vocal hygiene accompanied by VUR to help develop healthier use of the voice, facilitate healing, and prevent further/future injury or disorder. [ABSTRACT FROM AUTHOR]

Introduction: The impact of long-COVID-19 syndrome is rather variable, since it is influenced by several residual confounders. This study aimed to investigate the prevalence of long COVID-19 in healthcare workers (HCWs) from four university hospitals in north-eastern Italy: Trieste, Padua, Verona, and Modena-Reggio Emilia. Methods: During the period June 2022–August 2022, HCWs were surveyed for past COVID-19 infections, medical history, and any acute as well as post-COVID-19 symptoms. The prevalence of long COVID-19 was estimated at 30–60 days or 61+ days since first negative swab following first and second COVID-19 episode. Furthermore, the risk of long COVID-19 was investigated by multivariable logistic regression. Results were expressed as the adjusted odds ratio (aOR) with a 95% confidence interval (95%CI). Results: 5432 HCWs returned a usable questionnaire: 2401 were infected with SARS-CoV-2 at least once, 230 were infected at least twice, and 8 were infected three times. The prevalence of long COVID-19 after a primary COVID-19 infection was 24.0% at 30–60 days versus 16.3% at 61+ days, and 10.5% against 5.5% after the second SARS-CoV-2 event. The most frequent symptoms after a first COVID-19 event were asthenia (30.3%), followed by myalgia (13.7%), cough (12.4%), dyspnea (10.2%), concentration deficit (8.1%), headache (7.3%), and anosmia (6.5%), in decreasing order of prevalence. The risk of long COVID-19 at 30–60 days was significantly higher in HCWs hospitalized for COVID-19 (aOR = 3.34; 95%CI: 1.62; 6.89), those infected with SARS-CoV-2 during the early pandemic waves—namely the Wuhan (aOR = 2.16; 95%CI: 1.14; 4.09) or Alpha (aOR= 2.05; 95%CI: 1.25; 3.38) transmission periods—and progressively increasing with viral shedding time (VST), especially 15+ days (aOR = 3.20; 95%CI: 2.07; 4.94). Further determinants of long COVID-19 at 30–60 days since primary COVID-19 event were female sex (aOR = 1.91; 95%CI: 1.30; 2.80), age >40 years, abnormal BMI, or administrative services (reference category). In contrast, HCWs vaccinated with two doses before their primary infection (aOR = 0.57; 95%CI: 0.34; 0.94), undergraduate students, or postgraduate medical trainees were less likely to experience long COVID-19 at 30–60 days. Apart from pandemic waves, the main determinants of long COVID-19 at 30–60 days were confirmed at 61+ days. Conclusions: The risk of long COVID-19 following primary infection increased with the severity of acute disease and VST, especially during the initial pandemic waves, when more virulent viral strains were circulating, and susceptibility to SARS-CoV-2 was higher since most HCWs had not been infected yet, COVID-19 vaccines were still not available, and/or vaccination coverage was still building up. The risk of long COVID-19 therefore decreased inversely with humoral immunity at the individual level. Nevertheless, the prevalence of long COVID-19 was remarkably lower after SARS-CoV-2 reinfections regardless of vaccination status, suggesting that hybrid humoral immunity did not increase protection against the syndrome compared to immunity mounted by either natural infection or vaccination separately. Since the risk of long COVID-19 is currently low with Omicron and patients who developed the syndrome following SARS-CoV-2 infection in the early pandemic waves tend to return to a state of full health with time, a cost-effective approach to screen post-COVID-19 symptoms during the Omicron time could be restricted to vulnerable individuals developing severe disease and/or with prolonged VST.

Asthenia and fatigue are the most common syndromes in patients with liver disease, which significantly affects their quality of life. The prevalence of fatigue in chronic liver diseases is from 50% to 85%. While some progress has been made in understanding the processes that can cause fatigue in general, the underlying causes of fatigue associated with liver disease remain not well understood. In particular, many data suggest that fatigue associated with liver disease likely results from changes in neurotransmission in the brain against the background of hyperammonemia. Hyperammonemia is a metabolic state characterized by an increased level of ammonia, a nitrogen-containing compound. The present review describes hyperammonemia, which is likely important in the pathogenesis of fatigue associated with liver disease. Ammonia is a potent neurotoxin, its elevated blood levels can cause neurological signs and symptoms that can be acute or chronic, depending on the underlying pathology. Hyperammonemia should be recognized early, and immediately treated to prevent the development of life-threatening complications, such as, swelling of the brain and coma. The article gives pathophysiological mechanisms of influence of hyperammonemia on state of psychovegetative status of patients with liver diseases, also lists basic principles of treatment. A significant part of the article is devoted to L-ornithine-L-aspartate, which is effective in asthenia and fatigue to reduce the level of hyperammonemia through a variety of well-studied mechanisms in chronic liver diseases.

Introduction. One of the characteristic manifestations of COVID-19 is a disorder of smell, which, according to the literature, occurs in 61.2% - 85.6% of patients with COVID-19. The article discusses the problems of post-viral dysosmia in COVID-19 convalescents. Purpose of the study. Evaluation of olfactory disorders in patients after coronavirus infection and the possibility of obtaining additional benefits from prescribing bioregulatory medicine drugs.Materials and methods. The assessment of the severity of olfactory disorders in patients, taking into account the age according to self-assessment data using a visual analogue scale, as well as an objective assessment of odor identification using the Sniffin ‘Sticks Screening 12 Test. The possibility of increasing the efficiency of recovery of olfactory disorders by prescribing complex preparations of bioregulatory therapy (main group) was studied.Results. The percentage of persons who fully restored the olfactory function in the main group was 56.5%, while in the patients of the control group only in 6.6%. Faster (on the 7th day) dynamics of identification testing using SST-12 in patients taking complex preparations of bioregulation therapy was noted. On the 3rd day of therapy, there was a significant decrease in anxiety in patients treated with bioregulatory drugs.Discussion. The conducted study objectively confirmed that the olfactory disorder is present in the vast majority of patients with ARS. The appointment of bioregulatory therapy contributes to the early restoration of the olfactory function.Conclusions. Based on the results of this study, it can be concluded that it is advisable to use bioregulatory drugs.

This article examines how everyday encounters with kidney disease treatment in Sri Lanka's dry zone generate distinct space‐times of liminality. Building on work that explores the alternative coordinates of biopolitical intervention, I argue that health improvement schemes in the dry zone yield complex materialisations of "living death" in conditions of austerity, poverty, and aridity. Specifically, I illustrate how intervention reconfigures body‐ecologies, dismantles infrastructures of liveability, and re‐works relations between life and time in order to stabilise liminal forms of existence. Drawing on 15 months of ethnographic data, I describe two space‐times of liminality that emerge through experiences of treatment: the "zombie" and "life in the bubble". As part of my analysis, I document how these bodily states are ambiguously configured by experiences of care. Across these encounters, I illustrate how patients toggle back and forth between states of debility and capacity in ways that blur boundaries between life/death and bodies/environments. [ABSTRACT FROM AUTHOR]

Asthenia is a clinical syndrome that can be manifest in almost all somatic, infectious, and neurological diseases. Initially a protective mechanism indicating depletion of energy resources, asthenia can become a pathological and extremely disabling condition, and can even progress to an independent immune-mediated disease – chronic fatigue syndrome. Asthenia is often combined with affective and cognitive disorders, producing diagnostic difficulties. The article addresses the complex interweaving of asthenia, chronic fatigue syndrome, and cognitive and affective disorders. [ABSTRACT FROM AUTHOR]

Background: Metastatic breast cancer (MBC) is an incurable disease and its treatment focuses on prolonging patients' (pts) overall survival (OS) and improving their quality of life. Eribulin is a microtubule inhibitor that increases OS in pre-treated MBC pts. The most common adverse events (AEs) are asthenia, neutropenia and peripheral neuropathy (PN).Methods: PAINTER is a single arm, phase IV study, aimed at evaluating the tolerability of eribulin in MBC pts. Secondary objectives were the description of treatment efficacy and safety, the assessment of the incidence and severity of PN and its association with genetic polymorphisms. Genomic DNA was isolated from blood samples and 15 Single Nucleotide Polymorphisms (SNPs) were genotyped by Taqman specific assays. The association between PN and SNPs were evaluated by Fisher exact test.Results: Starting from May 2014 until June 2018 180 pts were enrolled in this study by 20 Italian centers. 170 of these pts could be evaluated for efficacy and toxicity and 159 for polymorphisms analysis. The median age of pts was 60 years old and the biological subtypes were luminal type (64.7%), Her2 positive (18.3%) and triple negative (17%). Pts were pretreated with a median of 5 lines for MBC. The median follow up of this study was 15.4 months with a median number of 4.5 cycles administered (minimum-maximum 1-23). The median overall survival was 12 months. 48.8% of pts experienced a dose reduction, mainly for neutropenia (23.9%) and liver toxicity (12%). 65 pts (38.2%) reported at least one severe toxicity. Neutropenia and neurotoxicity were the most frequent severe AEs (15.3% and 14.7%, respectively); other reported toxicities were osteo-muscular, abdominal or tumor site pain (19.4%), liver toxicity (6.6%), pulmonary toxicity (6.5%) and dermatological toxicity (3.6%). Among the 15 evaluated SNPs, an association with PN was found for rs2233335 and rs7214723.Conclusions: Eribulin is a well-tolerated treatment option in MBC. Schedule and dosage modifications were common, but toxicity rarely led to treatment discontinuation. SNPs rs2233335 (G/T and T/T) in the NDRG1 gene and rs7214723 (CC and CT) in the CAMKK1 gene were associated with PN. These findings, if validated, could allow a tailored treatment with eribulin in cancer patients.Trial Registration: ClinicalTrials.gov ID: NCT02864030. [ABSTRACT FROM AUTHOR]

This study reviews the working conditions of the miners of Corral Quemado, near Andacollo in the Coquimbo region of northern Chile, during the extraction and processing of manganese between 1941 and 1969. The extractivism's extraction techniques, mineral processing methods, and mining policies are presented and discussed. The poor working conditions in the mines led to significant manganese overexposure, resulting in a condition known as 'manganese madness' in the miners. Prolonged exposure to manganese causes several health complications that affect the central nervous system, resulting in psychomotor problems, body stiffness, involuntary movements, and facial spasms, in addition to psychological issues (compulsive behavior, emotional lability, and hallucinations, among others). Given that the negative effects of manganese poisoning, which were first reported in Europe in 1837, were already well known, the historiography and health condition of the Andacollo miners require attention. The Andacollo miners' precarious working conditions and the manganese toxicity created lasting mining and economic issues, and left a permanent imprint on the miners' bodies. At the time, miners' dramatic working conditions and disabling injuries prompted a series of parliamentary petitions aimed at improving their working conditions. [ABSTRACT FROM AUTHOR]

A booster dose after primary COVID-19 vaccination series was considered crucial after the emergence of the B.1.617.2 (Delta) and B.1.1.529 (Omicron) variants. Active surveillance was used to investigate reporting of adverse events post-booster dose of either of the licensed mRNA Comirnaty (Pfizer/BioNTech) or Spikevax (Moderna) vaccines in adult (17 years and older) recipients in central Italy. Eligible participants were enrolled and interviewed via phone using a structured questionnaire. Primary outcomes related to the occurrence of adverse events post-booster were stratified by vaccine, and frequency of local/systemic, mild/moderate/severe events. Of a total of 622 participants interviewed, 554 (89.1%) reported at least one adverse event (88.2% and 92.9% after the Comirnaty or Spikevax vaccine, respectively): 63.4% were female, and 78.5% aged 17 to 64 years, regardless of vaccine. 87.7% and 68.2% of all recipients described at least one local or systemic reaction, respectively: 97.3, 38.6 and 4.7% reported mild, moderate, or severe events, respectively. The most frequent adverse reactions were pain, redness, or swelling at the injection site and fatigue, while malaise and fever significantly occurred after the Comirnaty, and vomiting after the Spikevax booster. Compared to the primary vaccination, lymphadenopathy was more common after the booster (p < 0.001), especially after Comirnaty vaccine. The study findings revealed no serious or unexpected adverse events, and are in agreement with data available on booster dose for both mRNA vaccines. The transient, mild to moderate, and common to very common side reactions reported should be used to reassure potential recipients of the lack of safety concerns. [ABSTRACT FROM AUTHOR]

This article analyzes the results of the clinical and psychometric study of asthenia in foreign applicants for higher medical education at different stages of training. The study involved 110 applicants of the preparatory department (group 1) and 44 applicants of the I-II course (group 2). They were trained at Dnipro State Medical University. Duration of training was from 1 to 2 months and from 6 months to 2 years, respectively (at the time of participation in the study). The clinical and psychopathological examination was conducted using the semi-structured interview method and the psychometric investigation of the level of asthenia with using the Multidimensional Fatigue Inventory scale (MFI-20). It was found that the investigated group 2 had the significantly higher frequency of detection of both complaints/symptoms and nosological forms (by 1.8 times) than group 1. The analysis of the MFI-20 scale data confirmed the clinically obtained results: the normal (24,5%) and moderate level (23,5%) of asthenia was significantly more often observed in group 1. The high level (32%) of asthenia was in group 2 that proves the maladaptive process deepening. The obtained result indicates the necessity to develop preventive, differential and corrective measures to improve the quality of life of this contingent. [ABSTRACT FROM AUTHOR]

Background The phase II TALAPRO-1 study (NCT03148795) demonstrated durable antitumor activity in men with heavily pretreated metastatic castration-resistant prostate cancer (mCRPC). Here, we detail the safety profile of talazoparib. Patients and Methods Men received talazoparib 1 mg/day (moderate renal impairment 0.75 mg/day) orally until radiographic progression, unacceptable toxicity, investigator decision, consent withdrawal, or death. Adverse events (AEs) were evaluated: incidence, severity, timing, duration, potential overlap of selected AEs, dose modifications/discontinuations due to AEs, and new clinically significant changes in laboratory values and vital signs. Results In the safety population (N = 127; median age 69.0 years), 95.3% (121/127) experienced all-cause treatment-emergent adverse events (TEAEs). Most common were anemia (48.8% [62/127]), nausea (33.1% [42/127]), decreased appetite (28.3% [36/127]), and asthenia (23.6% [30/127]). Nonhematologic TEAEs were generally grades 1 and 2. No grade 5 TEAEs or deaths were treatment-related. Hematologic TEAEs typically occurred during the first 4-5 months of treatment. The median duration of grade 3-4 anemia, neutropenia, and thrombocytopenia was limited to 7-12 days. No grade 4 events of anemia or neutropenia occurred. Neither BRCA status nor alteration origin significantly impacted the safety profile. The median (range) treatment duration was 6.1 (0.4-24.9) months; treatment duration did not impact the incidence of anemia. Only 3 of the 15 (11.8% [15/127]) permanent treatment discontinuations were due to hematologic TEAEs (thrombocytopenia 1.6% [2/127]; leukopenia 0.8% [1/127]). Conclusion Common TEAEs associated with talazoparib could be managed through dose modifications/supportive care. Demonstrated efficacy and a manageable safety profile support continued evaluation of talazoparib in mCRPC. ClinicalTrials.gov identifier NCT03148795 [ABSTRACT FROM AUTHOR]

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Long COVID is an emergent, heterogeneous, and multisystemic condition with an increasingly important impact also on the pediatric population. Among long COVID symptoms, patients can experience chronic gastrointestinal symptoms such as abdominal pain, constipation, diarrhea, vomiting, nausea, and dysphagia. Although there is no standard, agreed, and optimal diagnostic approach or treatment of long COVID in children, recently compounds containing multiple micronutrients and lactoferrin have been proposed as a possible treatment strategy, due to the long-standing experience gained from other gastrointestinal conditions. In particular, lactoferrin is a pleiotropic glycoprotein with antioxidant, anti-inflammatory, antithrombotic, and immunomodulatory activities. Moreover, it seems to have several physiological functions to protect the gastrointestinal tract. In this regard, we described the resolution of symptoms after the start of therapy with high doses of oral lactoferrin in two patients referred to our post-COVID pediatric unit due to chronic gastrointestinal symptoms after SARS-CoV-2 infection. [ABSTRACT FROM AUTHOR]

Background: Thyroidectomy is a common procedure all over the world. Its complication rate is low, but some patients complain of weight gain and/or asthenia. The aim of this review is to investigate the correlation between thyroidectomy and weight change and asthenia. Materials and Methods: Seven papers concerning weight gain and four concerning asthenia were found. Results: Weight gain would seem to be more related to the change in habits after surgery. Asthenia seems to be more linked to endocrine mechanisms not yet clarified although a deficiency of triiodothyronine and its metabolites could explain some of its aspects. Conclusion: Patients who are candidates for thyroidectomy should be adequately informed of the onset of both possible implications of the surgical act in terms of weight gain and chronic asthenia. [ABSTRACT FROM AUTHOR]

The elderly has the physiological characteristics of insufficient essence and qi, declining original qi, and overall deficiency of the four channels and five zang organs, as well as the pathological characteristics of deficiency in the root and excess at the tip, the deficiency-excess complexity, and lingering pathogenic factors due to deficient healthy qi. The kidney, mingmen and triple jiao are physiologically interrelated and complement each other in function. Together with the five zang organs and six fu organs, they play the role of qi transformation as a whole. The deficiency of kidney essence and the decline of mingmen fire are the root causes of age-related debility, while the failure of qi transformation of the triple jiao is the key for transformation between deficiency and excess patterns. From the perspective of “kidney- mingmen-triple jiao qi transformation”, we analyze the TCM pathogenesis and symptoms of debility. Specifically, as the kidney fails to store essence, kidney deficiency may occur; as the kidney is not in charge of the external, pathogenic factors tend to invade the body; when the kidney fails to produce marrow, the spirit may not gather; simultaneously, the triple jiao fails to support qi transformation normally. As a result, a deficiency pattern tends to be complicated with an excess one with lingering pathogenic factors. Such an interpretation may contribute to the deep understanding of the linkage of “essence-qispirit- physique” in age-related debility and the establishment of a correlative dynamic pathogenesis for the condition. [ABSTRACT FROM AUTHOR]

Objectives: Investigating the prevalence of speech and language disorders and the contributing factors can help determine the best treatment options suited to the needs of these patients. So far, no comprehensive study has been conducted on screening speech and reading disorders and Problems in the Structure and Function of Articulation Organs (PSFAOs) in children in Mashhad City, Iran. This study aims to screen for these disorders and investigate the effects of demographic factors on such disorders. Methods: Via the stratified-cluster sampling method, 2770 native Persian-speaking children participated in this study, of whom 1381 were girls and 1389 were boys, ranging from preschool to the third grade (3 to 9 years old). After obtaining the demographic information, the PSFAOs screening was performed for all participants using a semi-structured questionnaire taken from Paul et al.'s report (2017). Screening for a grade of dysphonia was then carried out for children with suspected voice disorders using the grade, roughness, breathiness, asthenia, and strain test. Fluency of speech screening for children with suspected fluency disorders was performed using the stuttering severity instrument - fourth edition test, and screening of reading skills for school children was performed using the screening inventory reading test. Analytical analysis was performed via the Chi-square test between study variables, including disorders and other variables. Two types of logistic regression models were used. The data were analyzed using survey data analysis of the Stata software, version 14.1, and P<0.05 was considered significant. Results: The prevalence of articulation disorders, voice disorders, stuttering, PSFAOs, reading disorders, and multiple disorders (presence of two or more disorders per person) was 1.62%, 1.99%, 1.69%, 1.1%, 8.21%, and 14.89%, respectively. Descriptive analysis showed that the prevalence of articulation disorders, voice disorders, stuttering, and multiple disorders was higher in boys compared to girls (P=0.000), while the prevalence of reading disorders and PSFAOs was higher in girls (P=0.000). Furthermore, articulation disorders and reading disorders were more common in first-graders. The prevalence of voice disorders, stuttering, and PSFAOs were higher in the third graders. The logistic regression analysis showed that boys were more likely to develop speech and language disorders compared to girls (OR=1.3, P=0.01), and first-, second-, and third-graders were less likely to have such disorders when compared to preschoolers (OR=0.8, P=0.03). Discussion: Compared to previous studies, the different rates of prevalence of the disorders studied in this investigation are related to differences in their methodology, the number of samples, age, linguistic and cultural characteristics of the subjects, and individual factors. In this study, the prevalence of the studied disorders was higher in boys, first-graders, and children with families of 4 or more. The development of speech and language skills is different between genders; slower maturation of male brains seems to predispose them to slower development of speech skills. The lower prevalence in school-age children may be because these disorders gradually resolve during the early years of childhood. Moreover, low family socioeconomic status and family size may be the contributing factors to speech and language disorders. [ABSTRACT FROM AUTHOR]

This article examines the contestation of myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS). Lacking consistent diagnostic definitions, agreed‐on biological indicators, or approved treatments, ME/CFS is an incompletely medicalized condition. It is defined by intractable and debilitating exhaustion after any form of exertion. Through an ethnographic exploration of an American ME/CFS patient activist group, I develop the concept of "recursive debility." Symptoms form the very basis for disease activist groupings in the absence of biomarkers, but they also present a significant barrier to traditional forms of activism. Ironically, then, debilitation blocks the means through which debilitation might end. Patients contest systems of knowledge but always in bodies that experience exhaustion without end. This article presents a disability studies intervention in suggesting that the recursivity of debility demonstrates the profound interdependence of the bodily aspects of impairment and the sociopolitical aspects of disability. [ME/CFS, chronic illness, medicalization, symptoms, debility] [ABSTRACT FROM AUTHOR]

Peasant women in Cajamarca, Peru, who were sterilized by the Peruvian government in the 1990s, narrate their experiences of reproductive abuse using Andean medical principles of debilidad and fuerza (debility and strength) (Tapias 2006). In their narratives, many describe a generalized sense of loss of strength resulting from the procedure. This contrasts with the reproductive rights framework's emphasis on infertility as the main harm. In this article, I ponder the dissonance between these two frameworks and propose the concept of debilitated lifeworlds as decolonial feminist delinking (Mignolo 2007) from human fertility‐centric narratives. This concept is methodologically significant as a decolonial attunement to local motifs to talk about abuse and for weaving a constellation of embodied, emotional, social, and family harms. This article contributes to the emerging field of "decolonial reproductive studies" (Smietana et al. 2018: 117). [ABSTRACT FROM AUTHOR]

Introduction. In addition to acute manifestations, coronavirus infection is characterized by long-lasting symptoms: asthenia, somatic vegetative manifestations, sleep disorders and psychoemotional background, the question of therapeutic correction of which is especially relevant.The aim of the study was to study the mental, somatoform and cognitive aspects of anxiety disorders after coronavirus infection during treatment with tofizopam (Grandaxin®) at 150 mg / day.Materials and methods. The study involved patients who had a new coronavirus infection, who 4 weeks after the end of treatment for the underlying disease had complaints that suggest the presence of an anxiety disorder. The Hamilton scale was used to assess the level of anxiety. The patients were examined before the start of treatment, after 2, 4 and 6 weeks of therapy.Results. Prior to the start of therapy, all patients had an overall high level of anxiety: the average HAM-A score was 31.72 ± 2.24 points. At the end of Grandaxin® therapy, all patients showed a decrease in the level of anxiety: the average score for HAM-A was 12.68 ± 2.04 points (p distinct – the average score on the “cognitive disorders” subscale decreased three times – from 1.6 ± 0.12 to 0.5 ± 0.09 (p˂0.001).Conclusions. Disorders of the psychoemotional background (more often in the form of increased personal anxiety), sleep disorders, autonomic disorders, asthenic syndrome significantly affect the quality of life of patients who have suffered a new coronavirus infection. A comprehensive approach is needed in the clinical diagnosis of the long-term consequences of a new coronavirus infection and their subsequent correction with drug therapy.

Background: Auditory-perceptual evaluation of dysphonic voice is an essential clinical activity that characterizes the nature of dysphonia and aids in planning its clinical management. Although there are multidimensional acoustic measures that correlate well with overall severity ratings, they tend to include measures that have only small or moderate correlations with individual voice characteristics frequently perceptually measured (e.g., breathiness or roughness). Given this difference between perceptual and acoustic measures, it is unclear how much individual voice characteristics contribute to a listener's perception of overall severity of dysphonia. Purpose: The purpose of this study was to explore individual voice characteristics' relative contribution to the rating of overall dysphonia severity and to explore sex-related differences. Method: Two hundred ninety-six voice samples were accessed from the Perceptual Voice Qualities Database. Roughness, breathiness, asthenia, strain, pitch, and loudness ratings from the Grade, Roughness, Breathiness, Asthenia, Strain and Consensus Auditory-Perceptual Evaluation of Voice scales were used to predict overall voice quality severity in linear regression with bootstrapped coefficients. Results: Roughness, breathiness, and strain were the strongest predictors of overall severity. Asthenia and, to a lesser extent, pitch were also significant predictors of overall severity. Loudness was not a significant predictor. There were several sex-related differences noted, as well as differences related to the scale used. Conclusions: Breathiness, roughness, and strain were all important predictors of overall severity for all regressions. Clinicians should be aware of scale-related differences if they are using auditory-perceptual measures to choose voice therapy targets. Analyses accounting for perceptual strategy differences were recommended for future studies. [ABSTRACT FROM AUTHOR]

Persistent COVID-19 symptoms may be related to residual inflammation, but no preventive treatment has been evaluated. This study aimed to analyze, in a prospective cohort, whether corticosteroid use in the acute phase of COVID-19 in hospitalized patients may reduce the risk of persistent COVID-19 symptoms. A total of 306 discharged patients, including 112 (36.6%) from the ICU, completed a structured face-to-face assessment 4 months after admission. Of these, 193 patients (63.1%) had at least one persistent symptom, mostly dyspnea (38.9%) and asthenia (37.6%). One-hundred and four patients have received corticosteroids. In multivariable adjusted regression analysis, corticosteroid use was not associated with the presence of at least one symptom (OR=1.00, 95% CI: 0.58– 1.71, p=0.99) or with the number of persistent symptoms (p=0.74). Corticosteroid use remained ineffective when analyzing the ICU subpopulation separately. Our study suggests that corticosteroid use had no impact on persistent symptoms after COVID-19 in discharged patients. [ABSTRACT FROM AUTHOR]

Based on PROfound, olaparib is approved for patients with metastatic castration-resistant prostate cancer following disease progression on at least enzalutamide or abiraterone and who carry relevant alterations in DNA repair genes. To facilitate continued olaparib treatment as long as the patient derives benefit, we describe further safety assessments from PROfound focusing on the four most common adverse events (AEs) and events of special interest. Patients were randomized (2:1) to olaparib tablets (300 mg bid) or control (enzalutamide or abiraterone) until disease progression or unacceptable toxicity. Safety was assessed through AE reporting and laboratory assessments. Safety data were also collected from all patients in the control group who experienced radiographic disease progression and subsequently crossed over to olaparib treatment. 256 patients received olaparib and 130 control. Incidence rates for the four most commonly occurring AEs in the olaparib group (all-causality) were anaemia 50%, nausea 43%, fatigue/asthenia 42% and decreased appetite 31%. All were mostly Grade 1 and 2 and all peaked within the first 2 months of treatment as the events were managed where appropriate, primarily with dose interruptions or dose reductions. The extent of bone metastases at baseline or prior taxane use was not associated with the rate of anaemia. Pneumonitis was reported in 2% and 1.5% of patients in the olaparib and control groups, respectively, and one patient (0.4%) in the olaparib group experienced an event of MDS/AML after a 30-day follow-up period. Venous thromboembolic events occurred in 8% of olaparib and 3% of control patients. The four most common AEs observed in PROfound were generally manageable without the need for treatment discontinuation, allowing patients to remain on treatment for as long as they were deriving clinical benefit. gov registration number : NCT02987543. [Display omitted] • The safety profile of olaparib in men with mCRPC was similar to other solid tumours. • Events of anaemia, nausea, decreased appetite and fatigue occurred most frequently. • Incidences of all four events peaked within the first 2 months of starting treatment. • All four were generally manageable through dose modifications and supportive therapies. • Baseline bone metastases or prior taxane use was unrelated to the rate of anaemia. [ABSTRACT FROM AUTHOR]

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