In perioperative chemotherapy for breast cancer, dexamethasone (DEX) is administered at high dose to prevent adverse effects. Abrupt cessation of high-dose DEX treatment induces fatigue, but the incidence of the fatigue is uncertain. In this study, we retrospectively evaluated the incidence of fatigue following DEX administration for supportive therapy and the improvement of fatigue with DEX tapering, a gradual reduction of the daily dose, in breast cancer patients. The subjects were 124 patients with breast cancer receiving epirubicin- or docetaxel-based regimens as perioperative chemotherapy. Of all patients, 16.1% of patients experienced fatigue after cessation of DEX administration. The severity of fatigue was grade 1 in 6.5% of patients, grade 2 in 8.1% of patients, and grade 3 in 1.6% of patients. There were no significant differences in dose and duration of DEX administration between the group with fatigue and the group without fatigue. In almost all patients with fatigue, DEX tapering was performed from the next cycle. The efficacy of DEX tapering was evaluated by comparing the grade and subjective symptoms. Following DEX tapering, the severity of fatigue was significantly reduced (p < 0.05), and the subjective symptom was improved in 94.7% of patients. Therefore, fatigue is occasionally induced after the cessation of DEX administration for supportive therapy in breast cancer patients. The tapering of DEX may be effective for fatigue.

OBJECTIVE: Supportive therapy is key to prevent disease recurrence after peri-implantitis treatment. The primary objective was to quantify disease recurrence during supportive peri-implant therapy (SPIT) after peri-implantitis treatment. A secondary objective was to assess the success/failure of cumulative interceptive supportive therapy (CIST) after peri-implantitis treatment.
METHODS: Compliers (whether regular or erratic) with SPIT after peri-implantitis treatment during ≥12 months were retrospectively evaluated. CIST was prescribed whenever residual pockets ≥6 mm concomitant with profuse bleeding on probing (disease recurrence) were identified. Patient- and implant-related factors were analyzed to explore their associations with disease recurrence and the need for CIST.
RESULTS: Disease recurrence was considered in 28 patients (40 implants). Of these, 14 patients (23 implants) further demonstrated radiographic evidence of progressive bone loss (≥1 mm). This represented an overall disease recurrence following peri-implantitis treatment of ~20% and ~ 10% at patient and implant levels, respectively. Smokers, patients diagnosed at baseline with periodontitis grade C, and males were significantly more prone to exhibit recurrence. Patients undergoing CIST due to instability were not likely to respond favorably (~70% continued to exhibit residual pockets).
CONCLUSIONS: Disease recurrence during SPIT following peri-implantitis treatment on selected cases is ~20%. Patients undergoing CIST due to instability are not likely to respond favorably.

Protozoa exert a serious global threat of growing concern to human, and animal, and there is a need for the advancement of novel therapeutic strategies to effectively treat or mitigate the impact of associated diseases. Omega polyunsaturated fatty acids (ω-PUFAs), including Omega-3 (ω-3) and omega-6 (ω-6), are constituents derived from various natural sources, have gained significant attention for their therapeutic role in parasitic infections and a variety of essential structural and regulatory functions in animals and humans. Both ω-3 and ω-6 decrease the growth and survival rate of parasites through metabolized anti-inflammatory mediators, such as lipoxins, resolvins, and protectins, and have both in vivo and in vitro protective effects against various protozoan infections. The ω-PUFAs have been shown to modulate the host immune response by a commonly known mechanism such as (inhibition of arachidonic acid (AA) metabolic process, production of anti-inflammatory mediators, modification of intracellular lipids, and activation of the nuclear receptor), and promotion of a shift towards a more effective immune defense against parasitic invaders by regulation the inflammation like prostaglandins, leukotrienes, thromboxane, are involved in controlling the inflammatory reaction. The immune modulation may involve reducing inflammation, enhancing phagocytosis, and suppressing parasitic virulence factors. The unique properties of ω-PUFAs could prevent protozoan infections, representing an important area of study. This review explores the clinical impact of ω-PUFAs against some protozoan infections, elucidating possible mechanisms of action and supportive therapy for preventing various parasitic infections in humans and animals, such as toxoplasmosis, malaria, coccidiosis, and chagas disease. ω-PUFAs show promise as a therapeutic approach for parasitic infections due to their direct anti-parasitic effects and their ability to modulate the host immune response. Additionally, we discuss current treatment options and suggest perspectives for future studies. This could potentially provide an alternative or supplementary treatment option for these complex global health problems.

The emergence of coronavirus disease 2019 (COVID-19), caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), has affected many countries throughout the world. As urgency is a necessity, most efforts have focused on identifying small molecule drugs that can be repurposed for use as anti-SARS-CoV-2 agents. Although several drug candidates have been identified using in silico method and in vitro studies, most of these drugs require the support of in vivo data before they can be considered for clinical trials. Several drugs are considered promising therapeutic agents for COVID-19. In addition to the direct-acting antiviral drugs, supportive therapies including traditional Chinese medicine, immunotherapies, immunomodulators, and nutritional therapy could contribute a major role in treating COVID-19 patients. Some of these drugs have already been included in the treatment guidelines, recommendations, and standard operating procedures. In this article, we comprehensively review the approved and potential therapeutic drugs, immune cells-based therapies, immunomodulatory agents/drugs, herbs and plant metabolites, nutritional and dietary for COVID-19.

Mastitis is a major health problem for bovines and can be categorized as non-severe or severe, based on clinical symptoms. A severe case of clinical mastitis is usually defined by the cow being affected systemically. It is important to consider how to handle severe cases because these cases can be fatal and cause high production losses. However, there are generally few detailed treatment guidelines. By conducting a scoping review on the topic, we aimed to synthesize the information that is available on treatment and outcomes, as reported from clinical trials and observational studies. This was facilitated by following the PRISMA-guidelines with a stepwise systematic screening of scientific literature on the subject, retrieved via Pubmed and Web of Science, using pre-defined selection criteria. The results yielded a total of 14 reports of treatment and outcomes in cases of naturally occurring severe clinical mastitis. Cross-trial comparison was difficult due to the different exclusion criteria and outcome definitions. Many studies focused on cases caused by gram-negative bacteria treated with intensive antibiotic protocols, often containing antibiotics that are categorized as critical for human health. Few focused on severe cases caused by gram-positive bacteria or on the relative use of non-antibiotic treatment. In general, only a small number of statistically significant differences were found in trials comparing different treatment protocols, with no obvious trends across trials. Our findings emphasize the need for more research into the treatment efficacy of antibiotic and non-antibiotic options for clinically severe mastitis. Furthermore, consideration of how trial conditions relate to the practical circumstances in a field setting could improve the applicability of reported results. This could help to provide practitioners with the information needed to make evidence-based treatment decisions in cases of clinically severe mastitis.

OBJECTIVE: Gemcitabine and nab-paclitaxel (GnP) treatment, the standard first-line chemotherapy for unresectable pancreatic cancer, often causes peripheral neuropathy (PN). To develop alternative dosing strategies to avoid severe PN, understanding the relationship between pharmacokinetics (PK) and pharmacodynamics/toxicodynamics (PD/TD) is necessary. We established a PK-PD/TD model of GnP treatment to develop an optimal dose schedule.
METHODS: A mouse xenograft model of human pancreatic cancer was generated to measure drug concentrations in the plasma and tumor, antitumor effects, and PN after GnP treatment. The Simeoni tumor growth inhibition model with tumor concentrations and empirical indirect response models were used for the PD and TD models, respectively. Clinical outcomes were predicted with reported population estimates of PK parameters in cancer patients.
RESULTS: The PK-PD/TD model simultaneously described the observed tumor volume and paw withdrawal frequency in the von Frey test. For the standard GnP regimen, the model predicted clinical overall response (75.1%), which was overestimated compared to that in a recent phase II study (42.1%) but lower than the observed disease control rate (96.5%). Model simulation showed that dose reduction to less than 40% GnP dose was not effective; a change of dose schedule from every week for 3 weeks to every 2 weeks was a more favorable approach than dose reduction to 60% every week.
CONCLUSIONS: The PK-PD/TD model-based translational approach provides a guide for optimal dose determination to avoid severe PN while maintaining antitumor effects during GnP chemotherapy. Further research is needed to enhance its applicability and potential for combination chemotherapy regimens.

BACKGROUND: Patients with bipolar disorder (BD) are frequently exposed to traumatic events which worsen disease course, but this study is the first multicentre randomised controlled trial to test the efficacy of a trauma-focused adjunctive psychotherapy in reducing BD affective relapse rates.
METHODS: This multicentre randomised controlled trial included 77 patients with BD and current trauma-related symptoms. Participants were randomised to either 20 sessions of trauma-focused Eye Movement Desensitization and Reprocessing (EMDR) therapy for BD, or 20 sessions of supportive therapy (ST). The primary outcome was relapse rates over 24-months, and secondary outcomes were improvements in affective and trauma symptoms, general functioning, and cognitive impairment, assessed at baseline, post-treatment, and at 12- and 24-month follow-up. The trial was registered prior to starting enrolment in clinical trials (NCT02634372) and carried out in accordance with CONSORT guidelines.
RESULTS: There was no significant difference between treatment conditions in terms of relapse rates either with or without hospitalisation. EMDR was significantly superior to ST at the 12-month follow up in terms of reducing depressive symptoms (p=0.0006, d=0.969), manic symptoms (p=0.027, d=0.513), and improving functioning (p=0.038, d=0.486). There was no significant difference in dropout between treatment arms.
CONCLUSIONS: Although the primary efficacy criterion was not met in the current study, trauma-focused EMDR was superior to ST in reducing of affective symptoms and improvement of functioning, with benefits maintained at six months following the end of treatment. Both EMDR and ST reduced trauma symptoms as compared to baseline, possibly due to a shared benefit of psychotherapy. Importantly, focusing on traumatic events did not increase relapses or dropouts, suggesting psychological trauma can safely be addressed in a BD population using this protocol.

The time to administration of broad-spectrum antibiotics and (secondarily) to the initiation of hemodynamic stabilization are the most important factors influencing survival of patients with sepsis and septic shock; however, the basic prerequisite for the initiation of an adequate treatment is that a suspected diagnosis of sepsis is made first. Therefore, the treatment of sepsis, even before it has begun, is an interdisciplinary and interprofessional task. This article provides an overview of the current state of the art in sepsis treatment and points towards new evidence that has the potential to change guideline recommendations in the coming years. In summary, the following points are critical: (1) sepsis must be diagnosed as soon as possible and the implementation of a source control intervention (in case of a controllable source) has to be implemented as soon as (logistically) possible. (2) In general, intravenous broad-spectrum antibiotics should be given within the first hour after diagnosis if sepsis or septic shock is suspected. In organ dysfunction without shock, where sepsis is a possible but unlikely cause, the results of focused advanced diagnostics should be awaited before a decision to give broad-spectrum antibiotics is made. If it is not clear within 3 h whether sepsis is the cause, broad-spectrum antibiotics should be given when in doubt. Administer beta-lactam antibiotics as a prolonged (or if therapeutic drug monitoring is available, continuous) infusion after an initial loading dose. (3) Combination treatment with two agents for one pathogen group should remain the exception (e.g. multidrug-resistant gram-negative pathogens). (4) In the case of doubt, the duration of anti-infective treatment should rather be shorter than longer. Procalcitonin can support the clinical decision to stop (not to start!) antibiotic treatment! (5) For fluid treatment, if hypoperfusion is present, the first (approximately) 2L (30 ml/kg BW) of crystalloid solution is usually safe and indicated. After that, the rule is: less is more! Any further fluid administration should be carefully weighed up with the help of dynamic parameters, the patient\'s clinical condition and echo(cardio)graphy.
Die Zeiten bis zur Gabe eines Breitbandantibiotikums und (nachgeordnet) bis zum Beginn der hämodynamischen Stabilisierung sind die wichtigsten Einflussfaktoren für das Überleben von Patienten mit Sepsis und septischem Schock. Grundvoraussetzung für den Beginn einer adäquaten Therapie ist jedoch zunächst, dass die Verdachtsdiagnose „Sepsis“ gestellt wird. Die Behandlung der Sepsis ist daher, noch bevor sie begonnen hat, eine interdisziplinäre und interprofessionelle Aufgabe. Der vorliegende Artikel gibt eine Übersicht über den aktuellen „State of the Art“ der Sepsistherapie und weist auf neue Evidenz hin, die das Potenzial hat, die Leitlinienempfehlungen in den nächsten Jahren zu verändern.

The manuscript summarizes the consensus of the Austrian Society of Nephrology on the diagnosis and therapy of lupusnephritis, which is built on existing studies and literature. We discuss in detail the immunosuppressive treatment in proliferative forms of lupusnephritis (III and IV ± V) and in pure lupusnephritis V with nephrotic-range proteinuria. Furthermore, the supportive medication in lupusnephritis is summarized in the consensus. The figures were designed to provide the reader a guidance through the therapeutical approach in lupusnephritis for the daily practice.
UNASSIGNED: Das vorliegende Manuskript fasst die Empfehlungen der Österreichischen Gesellschaft für Nephrologie zur Diagnose und Therapie der Lupusnephritis zusammen und erläutert die Hintergründe der entsprechenden Empfehlungen anhand der vorhandenen Literatur. Wir besprechen im Detail die immunsuppressive Therapie in proliferativen Stadien der Lupusnephritis (Stadium III und IV mit/ohne Stadium V) und in der Lupusnephritis im reinen Stadium V mit großer Proteinurie. Zudem wird auch die konservative, supportive Therapie der Lupusnephritis detailliert besprochen. In den Abbildungen haben wir versucht, einen Leitfaden für die Praxis zur Therapie der Lupusnephritis zu erstellen.

The histopathological term focal-segmental glomerulosclerosis comprises different pathogenic processes with the unifying features of a high proteinuria and the name-giving glomerular lesion pattern seen on light microscopy. A differentiation according to the underlying cause into primary, secondary and genetic forms is therefore of utmost importance. The pathogenesis of primary focal-segmental glomerulosclerosis remains unknown but, like minimal-change disease, an autoimmune-mediated process leading to podocyte damage is assumed. Consequently, the unifying term \"podocytopathy\" is increasingly being used for both entities. Supportive treatment measures to preserve kidney function are important in all subtypes. In contrast, immunosuppressive treatment is only indicated in primary focal-segmental glomerulosclerosis. Steroid-dependence, steroid-resistance and frequently relapsing disease often complicate disease management and necessitate alternative treatment strategies. Here, the Austrian Society of Nephrology (ÖGN) provides consensus recommendations on how to best diagnose and manage patients with focal-segmental glomerulosclerosis.
UNASSIGNED: Der histopathologische Begriff fokal-segmentale Glomerulosklerose umfasst verschiedene Krankheitsprozesse mit dem gemeinsamen Kennzeichen einer großen Proteinurie und dem namensgebenden glomerulären Schädigungsmuster in der Lichtmikroskopie. Eine Einteilung in primäre, sekundäre und genetische Formen anhand der zugrundeliegenden Pathogenese ist daher von großer Relevanz. Die exakte Pathogenese der primären fokal-segmentalen Glomerulosklerose ist ungeklärt, allerdings wird – analog zur Minimal-change Glomerulopathie – eine autoimmun-vermittelte Schädigung der Podozyten angenommen. Angesichts des ähnlichen Pathomechanismus findet zunehmend die vereinende Bezeichnung „Podozytopathie“ Verwendung. Supportive Therapiemaßnahmen zum Erhalt der Nierenfunktion sind bei allen Formen angezeigt. Demgegenüber sollten immunsuppressive Therapien nur bei der primären fokal-segmentalen Glomerulosklerose zum Einsatz kommen. Komplizierte Verläufe umfassen steroid-abhängige, steroid-resistente und häufig relapsierende Formen und erfordern den Einsatz alternativer Therapiestrategien. Die Österreichische Gesellschaft für Nephrologie (ÖGN) stellt hier einen gemeinsamen Konsens darüber vor, wie erwachsene PatientInnen mit fokal-segmentaler Glomerulosklerose am besten diagnostiziert und behandelt werden können.