Course Of Therapy Research Articles

Effectiveness and Outcomes of Endoscopic Sinus Surgery for Nasal Polyps: A Systematic Review

Objectives: To investigate the effectiveness and outcomes of endoscopic sinus surgery (ESS) in patients with nasal polyps. Methods: A thorough search was conducted for pertinent literature using PubMed, SCOPUS, Web of Science, Science Direct, and Wiley Library. Rayyan QRCI was used throughout this extensive procedure. Results: Our results included nine studies with a total of 780 patients, and 490 (62.8%) were males. The follow-up duration ranged from 4 months to 24 months. All of the included patients underwent ESS for chronic sinusitis with nasal polyps (CRSwNP). Patients with CRSwNP and refractory CRSwNP reported better self-evaluated olfactory function after using ESS, experienced a higher reduction in polyp load, and better quality of life. Conclusion: Patients with CRSwNP reported significant improvements in quality of life and major symptoms when using ESS. The quality of the available data, as established in this evaluation, is low enough to make firm recommendations for the best course of surgical therapy. From a precision medicine perspective, high-quality studies are needed to phenotype these patients in order to identify which ones will benefit most from each type of medicinal and surgical therapy, including a combination of both, with long-term efficiency being a crucial result.

Treatment Strategy for Catamenial and Endometriosis-Related Recurrent Spontaneous Pneumothorax

RELEVANCE. The problem of treating thoracic endometriosis complicated by recurrent spontaneous catamenial pneumothorax is associated with the widespread prevalence of endometriosis, the complexity of its treatment and unsatisfactory long-term outcomes. The diagnosis of catamenial pneumothorax can only be established with a carefully collected history and confirmation of its recurrent nature. Favorable results are achieved with complex therapy carried out by the thoracic surgeon and gynecologist, consisting of an adequate volume of surgical intervention and hormonal therapy with gonadotropin releasing hormone agonists.AIM OF STUDY. To improve the diagnosis of thoracic endometriosis and recurrent catamenial and endometriosis-related spontaneous pneumothorax. To optimize the currently available treatment tactics by reducing the incidence of early relapses of catamenial pneumothorax and creating favorable conditions for the formation of reliable pleurodesis.MATERIAL AND METHODS. We studied the immediate outcomes of complex treatment of 30 patients (14.7%) with right-sided recurrent catamenial (28) and endometriosis-related spontaneous pneumothorax (2), with a median age of 41 (37;44) years, for the period from 2011 to the first half of 2023. Surgical treatment via video-assisted thoracoscopic access was performed in 26 patients (86.7%). After surgery, all the patients were recommended a six-month course of hormonal therapy with gonadotropin releasing hormone agonists.RESULTS. Various types of mechanical pleurodesis were performed in 25 patients (96.1%), resection of the diaphragm — in 17 (65.4%), alloplastic reconstruction with a synthetic mesh implant — in 12 patients (46.1%), pulmonary resection — in 9 (34.6%). In 12 of 26 patients (46.1%) in the early postoperative period, 6 (3; 6.75) days after surgery, a recurrence of catamenial pneumothorax developed, which subsequently required repeated interventions. In 5 patients, the relapse clearly coincided with the menstrual cycle. Early recurrence of pneumothorax required repeated drainage of the pleural cavity in all the patients, chemical pleurodesis in 2, and prolonged drainage of the pleural cavity in 1.CONCLUSION. Surgeries involving resection and reconstruction of the diaphragm with a mesh implant, pleurectomy, lung resection do not ensure the removal of all endometrioid heterotopias of the diaphragm and lung, therefore, during the first mensis after surgery, in the early postoperative period, 46.1% of the patients had a recurrence of catamenial pneumothorax, with no formed pleurodesis, which contributes to the possibility of further recurrences of pneumothorax. Improving the immediate outcomes of complex treatment of catamenial pneumothorax is possible with the preventive administration of hormonal therapy 1.5–2 months before the planned surgical intervention, which requires a multidisciplinary approach of the thoracic surgeon and gynecologist.

Therapeutic and Diagnostic Tactics for Metastases to the Lymph Nodes of the Neck without an Identified Primary Focus

Introduction. Metastatic squamous cell carcinoma from an unknown primary focus accounts for less than 5 % of malignant tumors in the head and neck. Improving the methods of diagnosis can reduce the incidence of this pathology. Materials and methods. A retrospective analysis of the results of diagnosis and treatment of 59 patients with metastasis to the lymph nodes of the neck without an identified primary focus was performed. The proportion of male patients was 86 % (51/59), female — 14 % (8/59). The average age of patients is 61 years. Squamous cell carcinoma prevailed — 79 % (47/59). Results. Metastatically affected lymph nodes were localized in 92 % of cases at levels II and III. The proportion of patients with stages N2, N3 prevailed — 55 % (abs. 26), 32 % (abs. 15), respectively. Overexpression of the P­16 protein in metastatically affected lymph nodes was detected in 70 %, PD­L1 in 48 %, and Epstein­Barr virus (EBV) in 6 %. Ipsilateral diagnostic palatine tonsillectomy of an apparently unchanged tonsil was performed in 15 % (9/59) of cases, revealing the primary site in one instance. Of the special treatment methods, complex and combined treatment prevailed — 55 % (abs. 26). Radiation therapy in an independent version was performed by 48 % of patients, while 76 % received the full course (abs. 16). Combined treatment (a course of Radiation therapy followed by chemotherapy) — in 7 % (abs. 3) 20 % of patients received polychemotherapy. Palliative immunotherapy (pembrolizumab 200 mg IV — 5 courses) was given to 1 patient. The average life expectancy was higher with complex treatment — it was 60 months (95 % CI 43.5–76.4), the median survival is 60 months. Discussion. The main methods of treatment of patients with metastases of squamous cell carcinoma without were radiation therapy in an independent version, as well as complex treatment. Ipsilateral diagnostic palatine tonsillectomy of an apparently unchanged tonsil was performed in 15 % (abs. 9), and allowed to identify the primary focus in 1 case.Conclusion. Metastasis to the lymph nodes of the neck without remains an urgent interdisciplinary problem. Prospective multicenter studies are required to improve and optimize the algorithms for diagnosis and treatment of these patients.

Granzyme B PET/CT Imaging Evaluates Early Response to Immunotherapy in Gastric Cancer.

In several malignancies, only a limited number of patients respond to immune checkpoint inhibitors. Predicting and monitoring responses to these inhibitors represent an unmet clinical need. Here, we developed a PET/CT probe targeting granzyme B, [68Ga]Ga-NOTA-Gly-Gly-Gly-Ile-Glu-Pro-Asp-CHO (GSI), and aimed to investigate whether it can be used to monitor the effects of immune checkpoint inhibitors early in the course of therapy. Methods: Seventy-two patients with gastric cancer (stages III-IV) were recruited for [68Ga]Ga-DOTA-GSI PET/CT imaging after 2 or 3 cycles of the immunotherapy, and 40 patients were included in the final analysis. The SUVmax of primary tumors (SUVmax-t), SUVmax of metastatic lymph nodes (SUVmax-LN), and SUVmax of normal tissues (liver and blood pool) were measured, and their target-to-liver background ratio (TLR) and target-to-blood background ratio (TBR) were denoted for primary tumors as TLRtumor and TBRtumor and for metastatic lymph nodes as TLRLN and TBRLN, respectively. The treatment responses were assessed within 1 wk after full-course treatment according to RECIST version 1.1. Wilcoxon rank-sum tests were used to compare the PET/CT parameters between responders and nonresponders. Receiver operating characteristic curve analysis was used to assess the diagnostic efficacy of [68Ga]Ga-DOTA-GSI PET/CT parameters in identifying responders. Two-tailed P value of less than 0.05 was considered statistically significant. Results: We found that SUVmax-t, TLRtumor, TBRtumor, SUVmax-LN, and TBRLN were higher in responders than in nonresponders (2.49 ± 0.58 vs. 1.55 ± 0.48, P = 0.000; 2.24 ± 0.48 vs. 1.74 ± 0.67, P = 0.007; 1.38 ± 0.43 vs. 0.90 ± 0.23, P = 0.000; 2.24 ± 0.99 vs. 1.42 ± 0.55, P = 0.003; and 1.28 ± 0.68 vs. 0.83 ± 0.32, P = 0.012, respectively). According to receiver operating characteristic curve analysis, the area under the curve for SUVmax-t, TBRtumor, TLRtumor, SUVmax-LN, TLRLN, and TBRLN was 0.886, 0.866, 0.746, 0.772, 0.648, and 0.731, respectively. The threshold of SUVmax-t was 2.05, and its sensitivity and specificity were 81.0% and 84.2%, respectively. In addition, multivariate logistic regression indicated that TBRtumor was an independent predictor of treatment response (P = 0.03). Conclusion: Our results indicated that [68Ga]Ga-DOTA-GSI PET/CT is a promising tool for predicting early response to combined immunotherapy in gastric cancer patients.

Using Biosensor Devices and Ecological Momentary Assessment to Measure Emotion Regulation Processes: Pilot Observational Study With Dialectical Behavior Therapy.

Novel technologies, such as ecological momentary assessment (EMA) and wearable biosensor wristwatches, are increasingly being used to assess outcomes and mechanisms of change in psychological treatments. However, there is still a dearth of information on the feasibility and acceptability of these technologies and whether they can be reliably used to measure variables of interest. Our objectives were to assess the feasibility and acceptability of incorporating these technologies into dialectical behavior therapy and conduct a pilot evaluation of whether these technologies can be used to assess emotion regulation processes and associated problems over the course of treatment. A total of 20 adults with borderline personality disorder were enrolled in a 6-month course of dialectical behavior therapy. For 1 week out of every treatment month, participants were asked to complete EMA 6 times a day and to wear a biosensor watch. Each EMA assessment included measures of several negative affect and suicidal thinking, among other items. We used multilevel correlations to assess the contemporaneous association between electrodermal activity and 11 negative emotional states reported via EMA. A multilevel regression was conducted in which changes in composite ratings of suicidal thinking were regressed onto changes in negative affect. On average, participants completed 54.39% (SD 33.1%) of all EMA (range 4.7%-92.4%). They also wore the device for an average of 9.52 (SD 6.47) hours per day and for 92.6% of all days. Importantly, no associations were found between emotional state and electrodermal activity, whether examining a composite of all high-arousal negative emotions or individual emotional states (within-person r ranged from -0.026 to -0.109). Smaller changes in negative affect composite scores were associated with greater suicidal thinking ratings at the subsequent timepoint, beyond the effect of suicidal thinking at the initial timepoint. Results indicated moderate overall compliance with EMA and wearing the watch; however, there was no concurrence between EMA and wristwatch data on emotions. This pilot study raises questions about the reliability and validity of these technologies incorporated into treatment studies to evaluate emotion regulation mechanisms.

An incomplete form of Kawasaki disease in a 2-month-old girl. How the diagnostic algorithm works in practice

BACKGROUND. Kawasaki disease is a rare, self-limiting inflammatory disease primarily affecting children under 5 years old. In 25 % of cases, it can lead to coronary artery aneurysms if not treated promptly with intravenous human immunoglobulin. A significant portion of Kawasaki disease patients present with an incomplete form, complicating diagnosis, while the risk of coronary artery aneurysms remains unchanged. Particularly vulnerable are infants under 6 months old, who may exhibit even more limited clinical symptoms, making them especially susceptible to severe cardiac complications. OBJECTIVE. To analyze a clinical case of an incomplete form of Kawasaki disease in a 2-month-old girl, raise awareness of Kawasaki disease, including its incomplete form, among healthcare workers in Ukraine, emphasize the critical importance of proper diagnostic evaluation of coronary arteries, and underscore the necessity of early administration of immunoglobulin when Kawasaki disease is suspected, even in the absence of pathological changes in the heart. MATERIALS AND METHODS. The study involved collecting medical history, physical examination data, laboratory and instrumental studies, and their analysis. The diagnosis of Kawasaki disease, including its incomplete form, was based on the 2017 recommendations of the American Heart Association. CLINICAL CASE. A 2-month-old girl presented with symptoms initially resembling a urinary tract infection, with no therapeutic response to multiple courses of antibacterial therapy. During the second week of illness, she developed swelling in her hands and feet, which, along with persistent fever, significant inflammatory response, and lack of improvement with antibiotics, led to the suspicion and diagnosis of Kawasaki disease based on the algorithm for incomplete Kawasaki disease. After administration of an immunomodulatory dose of intravenous human immunoglobulin at 2 g/kg on the 11th day of illness, there was a rapid regression of symptoms, normalization of inflammation markers, and overall improvement in the child's condition. By the second week of illness, small aneurysms of the right and left coronary arteries had formed but regressed within a few weeks from the onset of the disease. CONCLUSIONS. Kawasaki disease requires prompt therapeutic intervention and should be suspected in any child, especially those under one year of age, with a high fever lasting at least 5 days, unexplained by a preliminary diagnosis, and no response to antibiotic treatment in the presence of “bacterial” blood tests. Serial echocardiograms assessing coronary arteries, absolute dimensions, and Z-scores are mandatory.

Epidemiological and clinical aspects of syphilis incidence in the Russian Federation and the Kyrgyz Republic: comparative analysis

The Soviet period of development of domestic dermatovenereology was characterized by scientific achievements and the creation of organizational forms of combating venereal and contagious skin diseases. After the collapse of the USSR, socio-economic changes occurred in the former Soviet republics that affected the medical sphere. In recent years, the integration of dermatovenereologists with representatives of related specialties has increased and cooperation in the exchange of experience between dermatovenereological services of Russia and other countries is actively developing, including in the field of prevention of the spread of STIs. In 2021 and 2022, a significant increase (by 69.7%) in the incidence of syphilis was registered in Russia for the first time compared to 2020, which is due to an increase in this indicator among migrants (from 2801 cases in 2020 to 12748 cases in 2022), of which 30% of syphilis cases were among citizens of Kyrgyzstan. The article presents the results of a retrospective comparative study of syphilis incidence rates among children aged 0 to 14 years, adolescents aged 15 to 17 years, and adults over 18 years in the Russian Federation and the Kyrgyz Republic, and analyzes regulatory documents governing syphilis testing and treatment. Despite significant similarities in approaches to laboratory diagnostics of syphilis, including neurosyphilis, uniform principles of prenatal examination of women and treatment of pregnant women, there are currently a number of significant differences, including shorter courses of therapy and low doses of drugs, shorter periods of clinical and serological monitoring in the Kyrgyz Republic.

Evaluation of blood MSI burden dynamics to trace immune checkpoint inhibitor therapy efficacy through the course of treatment.

Analysis of serial liquid biopsy (LB) samples has been found to be a promising approach for the monitoring of tumor dynamics in the course of therapy for patients with colorectal cancer (CRC). Currently, somatic mutations are used for tracing the dynamics of the tumor via LB. However, the analysis of the dynamic changes in the molecular signatures such as microsatellite instability (MSI) is not currently used. We hypothesized that changes in blood MSI burden (bMSI) could be registered using serial LB sampling in the course of immune checkpoint inhibitors (ICI), and that its changes could potentially correlate with treatment outcomes. We report the preliminary findings of the observational trial launched to study (NCT06414304) the dynamics of bMSI in 9 MSI-positive CRC patients receiving ICI. NGS-based MSI testing was performed on both pre-treatment FFPE and serial LB samples. For patients who had detectable bMSI burden in any of the LB samples (n = 8, 89%), median bMSI was 1.4% (range, 0.01-40%). Among patients with detectable MSI in available FFPE samples, median MSI burden was 29.3% (range, 10-40%). bMSI detected in baseline LB and FFPE samples were positively correlated (Pearson's R 0.47). Maximal variant allele frequencies of driver mutations observed in LB were also positively correlated with bMSI burden (Pearson's R 0.7). Patients who had clinical benefit had undetectable bMSI burden at follow-up. Our results provide the rationale for further validation of bMSI as a predictive biomarker of ICI in MSI-positive patients.

Effectiveness of the Walkbot system in patients with infantile cerebral palsy

BACKGROUND: Estimating the effectiveness of robotic mechanotherapy is crucial in the rehabilitation of children with cerebral palsy. AIM: To evaluate the effectiveness of the Walkbot robotic complex (Walkbot, Korea) in children with cerebral palsy. MATERIALS AND METHODS: The study included 35 patients with infantile cerebral palsy who received courses of rehabilitation therapy based on the state autonomous institution “City Children’s Polyclinic No. 7.” A comparative analysis of the functional motor outcomes between two groups of children with cerebral palsy was performed. Group 1 was treated with locomotor therapy on the Walkbot, whereas group 2 was not prescribed with the apparatus. RESULTS: The effect of using the Walkbot mechanotherapeutic complex on functional motor outcomes in patients with infantile cerebral palsy was evaluated. Better dynamics of the level of motor skills development on the GMFM-66 scale was noted in group 1 (by 6.8% in group 1 and 4.1% in group 2; p=0.006). The Hauser index (p=0.05) indicated an improvement in locomotor function, which increased the level of independence in everyday life according to the FIM scale (p=0.044), compared to the data of children in the control group. Attaining the effect depends on the number of procedures and total number of rehabilitation courses. CONCLUSION: Children with cerebral palsy who received the Walkbot therapy have better motor outcomes, primarily relating to locomotor function.

Association of Granulocyte Colony-Stimulating Factor Treatment with Risk of Brain Metastasis in Advanced Stage Breast Cancer.

The routine use of granulocyte colony-stimulating factor (GCSF) is not recommended for the prevention or treatment of chemotherapy-induced neutropenia or febrile neutropenia because risks associated with certain types of cancers, distant organ metastases, and primary tumor growth cannot be excluded. We examined the association between GCSF use and the incidence of brain metastasis (BM), as well as BM-free survival (BMFS). This retrospective cohort study included 121 stage IV breast cancer patients without confirmed BM at the time of diagnosis and who received at least one course of systematic chemotherapy or target therapy at a tertiary teaching hospital between 1 January 2014 and 31 December 2022. The effect of GCSF use on BM was assessed with other confounding factors in Cox regression analyses. In this retrospective cohort, patients who received GCSF treatment had a significantly higher incidence of BM than those who did not (34.9% vs. 13.8%, p = 0.011). Univariate Cox regression analysis showed that GCSF use, menopause status, hormone treatment, HER2 treatment, cumulative dosage, dosage density, and neutropenia were independent risk factors for BMFS (p < 0.05). GCSF users had a higher risk of BM (adjusted HR: 2.538; 95% CI: 1.127-5.716, p = 0.025) than nonusers. BM risk was significantly associated with those with neutropenia (RR: 1.84, 95% CI: 1.21, 2.80) but not with those without neutropenia (RR: 0.59, 95% CI: 0.41-0.84, Interaction p-value < 0.05). The higher the dose density of GCSF, the higher the risk compared with those who do not use GCSF (p for trend < 0.01). These preliminary results suggest that GCSF is associated with BM in patients with stage IV breast cancer who did not have BM at initial diagnosis. Further comprehensively designed large-scale observational studies are needed to confirm our preliminary results.

A Novel Chimeric Oncolytic Virus Mediates a Multifaceted Cellular Immune Response in a Syngeneic B16 Melanoma Model

Background/Objectives: Oncolytic virotherapy is a promising approach in cancer immunotherapy. We have previously described a recombinant hybrid oncolytic virus (OV), VSV-NDV, which has a favorable safety profile and therapeutic immunogenicity, leading to direct oncolysis, abscopal effects, and prolonged survival in syngeneic in vivo tumor models. While OVs are known to mediate systemic anti-tumor immune responses, the detailed characterization of local and systemic immune responses to fusogenic oncolytic virotherapy remains unexplored. Methods and Results: We analyzed immune cell compartments in the spleen, blood, tumor-draining lymph nodes (TDLNs), and tumors over the course of VSV-NDV therapy in a bilateral syngeneic melanoma mouse model. Our results revealed significant local infiltration and activation of T lymphocytes in tumors and globally in the blood and spleen. Notably, in vivo CD8+ T cell depletion led to complete abrogation of the tumor response, highlighting the crucial role of T cells in promoting the therapeutic effects of oncolytic VSV-NDV. In vitro co-culture experiments enabled the interrogation of human immune cell responses to VSV-NDV-mediated oncolysis. Human peripheral blood mononuclear cells (PBMCs) were efficiently stimulated by exposure to VSV-NDV-infected cancer cells, which recapitulates the in vivo murine findings. Conclusions: Taken together, these data characterize a broad anti-tumor immune cell response to oncolytic VSV-NDV therapy and suggest that CD8+ T cells play a decisive role in therapeutic outcome, which supports the further development of this chimeric vector as a multimechanistic immunotherapy for solid cancers.

7236 Long Term Extension of Osilodrostat Therapy in Canadian Patients with Cushing’s Disease Benefiting from the LINC 3 and LINC 4 Studies

Abstract Disclosure: L.M. Martel: Other; Self; LMD receives partial fellowship salary support though educational grants from Recordati Rare Disease Canada Inc and Pfizer Canada. G. Houde: Other; Self; GH served as a consultant for Novartis. C. Chik: Other; Self; grants and/or consulting fees from Pfizer, Ipsen, Novartis and Novo Nordisk Canada. S.A. Imran: Other; Self; consulting fees from Pfizer, Recordati and Novartis. E. Paron: Other; Self; employees of Recordati Rare Disease Canada Inc. F. Lebel: Other; Self; employees of Recordati Rare Disease Canada Inc. A. Lacroix: Other; Self; reports grants and personal consulting fees from Novartis, Recordati and Pfizer. Introduction: Osilodrostat, a potent oral 11β-hydroxylase inhibitor, provided rapid, sustained cortisol normalization in Cushing’s disease (CD) patients in two Phase III trials (LINC 3, NCT02180217; LINC 4, NCT02697734); persistent biochemical and clinical improvement of CD were reported after 72 and 96 weeks of therapy, respectively (10.1530/EJE-22-0317; 10.3389/fendo.2023.1236465). After study completion and continued clinical benefit with osilodrostat, patients could transition in a roll-over study (CLCI699C2X01B , NCT03606408). As osilodrostat is now approved for therapy of CS in Europe and CD in USA, but not in Canada, seven Canadian patients who had benefited from osilodrostat were transitioned to an investigator initiated study ((ISS-CA-2023, NCT06131580). Objective: To analyze the course of therapy with osilodrostat which allowed long-term biochemical and clinical control of CD since initiation of LINC 3 and LINC 4 core studies for up to 105 months. Methods: Retrospective review of clinical, biochemical and imaging data were collected through chart review of 11patients enrolled in four Canadian centers in LINC 3 and 4 in LINC 4 parent studies. Seven patients remained in the roll-over study until termination and initiation of the Canadian study on October 24 2023. Data from initiation of therapy until October 24 2023 were analyzed. Results: Of the eleven enrolled patients, four discontinued treatment due to muscle cramps, repeat transsphenoidal surgery (TSS) for corticotroph adenoma progression in 2 cases, and hyperandrogenism and opting for bilateral adrenalectomy in one case. Seven cases (5 LINC 3 and 2 LINC 4) pursued therapy in the extension study: 2 men and 5 women, mean age 46 y.o. (range 28-72). All but one had previous TSS, one Gamma Knife and 4 received previous medical therapy. The median 24 hour urinary free cortisol (UFC) before starting osilodrostat was 334 nnmol/d (2.4 x ULN; range 133-414). The median treatment duration was 82 months (range 67-105) and median time to normalize UFC was 36 days. The median maximal dose required to normalize UFC was 10 mg/day (4-60); dose was frequently reduced because of symptoms of relative cortisol withdrawal or adrenal insufficiency (n: 5) to 6.5 mg/day (range: 1 mg every 6 days to 30 mg/d) currently. Last median UFC was 60 nmol/d (range 22-154; 6/7 in normal range &amp;lt; 138nmol/d). Tumor growth occurred in 1 patient (2mm). All patients presented partial to complete improvement of CD features, whereas one patient developed moderate clinical hyperandrogenism, hypertension and borderline prolongation of QTc that normalized after a dose reduction. Conclusions: Osilodrostat can provide sustained biochemical and clinical control of hypercortisolism in patients with CD for up to 9 years; however drug efficacy and dose requirement varies greatly between patients and must be adjusted carefully and regularly during course of therapy. Presentation: 6/3/2024

Study protocol TransTAM: Transdiagnostic research into emotional disorders and cognitive-behavioral therapy of the adaptive mind

BackgroundEmotional disorders such as depression and anxiety disorders share substantial similarities in their etiology and treatment. In recent decades, these commonalities have been increasingly recognized in classification systems and treatment programs crossing diagnostic boundaries.MethodsTo examine the prospective effects of different transdiagnostic markers on relevant treatment outcomes, we plan to track a minimum of N = 200 patients with emotional disorders during their routine course of cognitive behavioral therapy at two German outpatient clinics. We will collect a wide range of transdiagnostic markers, ranging from basic perceptual processes and self-report measures to complex behavioral and neurobiological indicators, before entering therapy. Symptoms and psychopathological processes will be recorded before entering therapy, between the 20th and 24th therapy session, and at the end of therapy.DiscussionOur results could help to identify transdiagnostic markers with high predictive power, but also provide deeper insights into which patient groups with which symptom clusters are less likely to benefit from therapy, and for what reasons.Trial RegistrationThe trial was preregistered at the German Clinical Trial Register (DRKS-ID: DRKS00031206; 2023–05-09).

Psychological burden and depressive symptoms in caregivers of hemato-oncological patients: the role of medical visits

AbstractInformal caregivers of patients with cancer are known to experience extensive burdens, whereas this issue remains unresolved in the setting of hematological malignancies. Yet, these diseases are characterized by a prolonged course, numerous relapses, and implementation of multiline therapy, administered in outpatient facilities. This study aimed to assess the factors contributing to burden and depressive symptoms in informal caregivers of patients with hematological malignancies, while concentrating on the role of medical visits. The study population comprised patients and their caregivers, recruited at the Rambam Hematology Ambulatory Unit. Participants completed validated questionnaires, including the Center for Epidemiologic Studies Depression Scale and the Zarit Caregiver Burden Interview. The cohort (n = 185) included 115 patients (average age, 62.8 ± 14.5 years; 54 males) and 70 caregivers. Among caregivers, 80% reported high psychological burden, and 50% reported significant depressive symptoms. The burden was higher if caregivers were females and if patients were less educated, less healthy, and more depressed. The caregiver burden and depressive symptoms were significantly linked, and the medical visit frequency predicted the level of both. The caregiver burden fully mediated the link between the independent variables of self-rated health and medical visits and the dependent variable of caregiver depressive symptoms. Informal caregivers of ambulatory patients with hemato-oncological malignancies experience high levels of psychological burden and depressive symptoms. This is partly attributed to the medical visit frequency. Hence, a decrease in the number and length of such visits via the implementation of advanced technology could essentially reduce burden and depressive symptoms of caregivers, without compromising patient outcomes.

The relationship between changes in pain intensity and functional disability in persistent disabling low back pain during a course of cognitive functional therapy.

Pain relief and reduced disability are both common treatment targets for persistent disabling low back pain (LBP). Cross-sectional studies show a moderate relationship between functional disability and pain intensity, but little is known about the relationship between changes in pain intensity and functional disability over multiple time points. The objective of this study was to investigate the associations between changes in functional disability and pain intensity and whether changes occurred simultaneously or differentially during a course of cognitive functional therapy for people with persistent disabling LBP. Self-reported measures of pain intensity and patient-specific functional disability were collected prior to each treatment session from 40 participants during a 12-week intervention period. Linear mixed modeling was used to assess simultaneous and lagged associations between pain intensity and functional disability over time. Sensitivity analysis using nonparametric subject-specific methods (simulation modeling analysis) was also performed. Thirty-five participants had sufficient data for analysis. Using the linear mixed-model approach, there was evidence of a moderate and simultaneous association between pain intensity and functional disability over time (regression coefficient = 0.56, 95% confidence interval: 0.44-0.68, p < 0.001). Simulation modeling analysis supported weak to mostly strong associations and supported for simultaneous change in pain and disability for the majority of participants (22 of 35, 64%). Changes in pain intensity and functional disability were moderately related across the intervention. Visual inspection of graphs indicated a very close relationship in some individuals and a decoupling of pain intensity and functional disability in others. The changes in pain intensity and functional disability seem to occur simultaneously in most individuals.

Advantages, disadvantages and optimization of organ-sparing methods for uterine fibroids treatment

Introduction. Uterine fibroids (UF) are benign monoclonal hormone-depended tumors originating from smooth myocytes of cervix or body uterus affecting up to 29 % of women aged 15–45 years worldwide. Taking into account the current demographic situation and annually increasing tendency for pregnancy planning at older reproductive age, an organ-sparing strategy is becoming a first-priority approach for UF treatment.Aim: to investigate efficiency of selective progesterone receptors modulators (SPRM) for UF treatment in women of reproductive age.Materials and Methods. A prospective cohort study involved 40 patients with UF at average age of 39.3 ± 5.8 years. Using simple randomization, the patients were divided into 2 groups per 20 subjects in each. The average age of the patients was comparable and comprised 38.15 ± 5.65 and 40.5 ± 5.8 years in groups 1 and 2, respectively (p = 0.203). In both groups, after assessing liver function tests in accordance with the instructions, a treatment course with SPRM group drug (ulipristal acetate) was used at a daily dose of 5 mg for 84 days (1 course) with an interval until the onset of second menstruation after drug withdrawal. Group 1 and group 2 subjects received 2 and 3 therapy courses, respectively. After each course, patients underwent control ultrasound examinations (UE) by analyzing uterus volume and diameter of dominant myomatous node along with liver tests. A temporal quantitation of the difference between UF and dominant node two sizes as well as the maximum uterine volume size and effect size assessment was expressed as the difference of means (Δ) with a 95 % confidence interval (CI).Results. Based on UE data, the uterus size in group 1 was enlarged to an average of 129.49 ± 75.57 cm3, the maximum size of dominant node was 38.9 ± 17.38 mm; in group 2, the uterus was as large as 294.83 ± 161.37 cm3 with maximum size of the dominant node of 53.33 ± 25.48 mm. After therapy in group 1, dominant node size was significant regressed: after therapy course 1 an effect size of quantitated difference between UF two sizes and the dominant node (Δ) was 8.70 (4.11; 13.29) mm (p &lt; 0.001). After therapy course 2 vs. therapy course 1, a size stabilization (Δ) was noted comprising 1.00 (–1.39; 3.39) mm (p = 0.390); the total effect (Δ) was 9.67 (–14.59; –4.75) mm (p &lt;0.001). In group 2, after therapy course 1, the dominant node also regressed, with effect size (Δ) of 9.49 (7.08; 11.89) mm (p = 0.001). The effect (Δ) after therapy course 2 vs. therapy course 1 in group 2 was more prominent reaching 10.74 (5.86; 15.61) mm (p = 0.001). However, after therapy course 3, a larger node size was observed compared to therapy course 2 – (Δ) 8.25 (0.67; 15.83) mm (p = 0.329). Despite the lack of pronounced negative dynamics, based on medical indications 9 patients in group 2 underwent uterine artery embolization to prevent disease relapse.Conclusion. SPRM therapy can be used both as an independent means for MM therapy and in combination with surgical interventions. Such an approach allows for some women to become pregnant without preceding myomectomy, whereas for those approaching age-related menopause to avoid surgical treatment and gently enter natural postmenopause. Currently, conservative and surgical treatment methods for leiomyomas should complement each other to achieve the best clinical outcomes.

Correlation Between Temporomandibular Joint Disorders and Bruxism: A Systematic Review and Meta-analysis

Background The common conditions bruxism and temporomandibular joint disorders (TMD) have a major impact on dental health and quality of life. Even though both disorders have been thoroughly examined, there is still discussion and research surrounding their association. Objective The purpose of this study was to investigate the relationship, possible risk factors, and therapeutic consequences of the interaction between bruxism and TMD. Methods To summarize the available data on the relationship between bruxism and TMD, a thorough literature review was carried out. Furthermore, information was gathered to look at the connection between TMD symptoms and self-reported bruxism. We searched several databases for the relevant literature. These included; PubMed, Cochrane Google Scholar, etc. Following the inclusion and exclusion criteria a group of researchers collaborated to “include” and “exclude” the studies and a total of n=11 studies were considered for final review and analyses. Results The primary endpoint of the current analysis was to evaluate the correlation between temporomandibular joint disorders and bruxism. 10/11 (91%) of the studies advocated for a significant correlation; whereas, only 1/11 (9%) favored that there is a negative association between the two. The overall Odds ratio value was =5.66, CI=95% (4.63-6.91). The overall heterogeneity was found to be Tau2=0.05; Chi2=26.00; df=8; I2=69%. The overall effect size was found to be, Z=16.97 (p&lt;0.00001) which was significant. Conclusion In conclusion, our research shows an important association between temporomandibular joint abnormalities and bruxism, emphasizing the significance of identifying and treating these diseases in clinical settings. When patients report similar symptoms, healthcare practitioners should think about screening for both bruxism and TMD. Multidisciplinary approaches may also be helpful for a thorough examination and course of therapy. To further inform preventive and treatment measures, more study is required to clarify the underlying processes and causal links between bruxism and TMD. Bangladesh Journal of Medical Science Vol. 23 No. 04 October’24 Page : 1008-1019

Longitudinal Health-Related Quality of Life Among Patients With High-Risk Pediatric Hodgkin Lymphoma Treated on the Children's Oncology Group AHOD 1331 Study.

PURPOSEThere have been no previous longitudinal assessments of health-related quality of life (HRQoL) during treatment for pediatric Hodgkin lymphoma (HL). The addition of brentuximab vedotin (BV) to a multidrug chemotherapy backbone demonstrated superior efficacy to standard chemotherapy for patients with pediatric high-risk HL in the AHOD 1331 trial. However, the impact on HRQoL is unknown.PATIENTS AND METHODSAfter treatment random assignment, 268 participants older than 11 years were enrolled in a prespecified, longitudinal, patient-reported outcomes substudy. HRQoL was assessed using the seven-item Child Health Ratings Inventories (CHRIs)-Global scale before treatment (T1) and at cycle 2 (T2), cycle 5 (T3), and end of treatment (T4). A clinically meaningful increase in HRQoL was considered 7 points on the CHRIs-Global. Multivariable linear regression estimated associations between demographic/clinical variables and HRQoL at T1. Linear mixed models estimated changes in HRQoL across the treatment arm.RESULTSParticipant characteristics were balanced by treatment arm. Ninety-three percent of participants completed the CHRIs at T1, 92% at T2, 89% at T3, and 77% at T4. At T1, female sex and fever (P < .05) were each associated with worse HRQoL. By T2, participants in the BV arm experienced a statistically and clinically significant improvement in HRQoL (β = 7.3 [95% CI, 3.2 to 11.4]; P ≤ .001), which was greater than the change in the standard arm (difference in change β = 5.1 [95% CI, -0.2 to 10.3]; P = .057). The standard arm did not experience a statistically or clinically significant increase in HRQoL until T4 (β = 9.3 [95% CI, 4.7 to 11.5]; P < .001).CONCLUSIONThese data demonstrate successful collection of serial HRQoL from youth with high-risk pediatric HL and improvement in HRQoL over the course of initial therapy, sooner and to a greater extent in the group receiving the novel agent BV.

Prediction of structure of mycobacterial efflux pump protein Rv0194 and molecular dynamics simulation of the predicted structures

Tuberculosis is a major cause of morbidity and mortality primarily in developing nations. The rising number of cases of multidrug resistance and extensive drug resistance are a critical concern for the management of the condition. Even though new antibiotics are being developed, eventually there are also strains that are resistant to them. The evolution of resistance in Mycobacterium tuberculosis is significantly influenced by drug efflux caused by efflux pumps. Rv0194 is an important efflux pump associated with resistance to multiple drugs like beta lactam antibiotics like ampicillin and also erythromycin and novobiocin. The introduction of efflux inhibitors for Rv0194 could shorten the course of current therapy and improve the efficacy of second-line medications. Building a trustworthy molecular model of this efflux pump is the goal of this study. We created 3 models using different modeling tools. These models were then subjected to a 20 ns molecular dynamics simulation in a lipid bilayer. We find that the model built by Swiss Model shows the best results in molecular modeling and validation and the structure is also stable throughout the 20 ns MD simulations. Consequently, this model is reliable and can be used for further studies.

SPECT/CT Quantification of 99m-TC PYP Uptake to Assess Tafamidis Treatment Response in ATTR Cardiac Amyloidosis

BackgroundCardiac imaging with bone-avid tracers for the diagnosis of ATTR cardiac amyloidosis employs only limited quantification, but SPECT/CT acquisition can provide volumetric assessment with quantification of tracer uptake. Tafamidis is routinely used in the treatment of cardiac amyloidosis but there is scant data on changes in imaging results during therapy. The purpose of this study was to perform longitudinal assessment of Tc-99m-PYP imaging to determine if tafamidis therapy results in any change in quantitative measures of tracer uptake. MethodsA prospective, single-center study of ATTR patients being treated with tafamidis using Tc-99m-PYP SPECT/CT to quantify cardiac tracer uptake in the whole heart and left ventricle. Standardized uptake values (SUVs) were adjusted for blood pool activity. Comparison of baseline activity was made to values obtained approximately every 6 months during treatment. ResultsTwenty-two patients (77.0 ± 7.5 years old, 86.4% male) were on tafamidis for 15.3 ± 4.0 months with an average time between baseline and final follow-up study of 16.8 ± 4.7 months. Thirteen (59.1%) had multiple follow-up amyloid studies. Statistically significant reductions in total SUVs, SUV volume, and percentage of injected dose were seen. Adjusted for the maximal aortic SUV, the total SUV’s in the left ventricle decreased by 36.9%, the SUV volume by 38.7%, and the percentage of injected dose decreased by 34.9% (all p-values ≤0.0001). Over the study duration there was a decrease of 7.7%/month in the measured metrics. ConclusionThe quantitative SUV measurements from Tc-99m-PYP SPECT/CT revealed an overall decrease in scintographic amyloid burden during the course of tafamidis therapy, but additional work is needed to determine the optimal metrics and improve the reproducibility of the quantification.