Healing beyond the joint: Addressing mental health in periprosthetic joint infection in a prospective longitudinal study.

OBJECTIVE: Periprosthetic joint infection (PJI) is a devastating complication following joint replacement surgeries. While the somatic impacts of PJI have been extensively explored, the influence on mental health remains understudied. This study aimed to longitudinally assess the psychological burden, quality of life, and expectations in individuals undergoing treatment for PJI. METHODS: A prospective study was conducted at a German trauma center between January 2020 and December 2022. Patients diagnosed with PJI (n = 29, mean age 71.4 ± 8.8 years) were assessed at five timepoints, within one week before revision surgery, one month, three, six, and twelve months postoperatively. Outcomes included the ICD-10 symptom-rating (ISR), German Short-Form 36 (SF-36), European Quality of Life 5 Dimensions (EQ-5D), and an expectation questionnaire. RESULTS: Psychological scores exhibited significant upward trends over time. The ISR score increased from 0.55 preoperatively to 0.87 at the 12-month follow-up (p = 0.002), surpassing the clinically relevant threshold. Depression and anxiety scores peaked at 6 months (1.6, p = 0.005) and 12 months (1.12, p = 0.001), respectively. Quality of life, measured by SF-36, showed stable physical component summary scores but declining mental component summary scores. Patients' expectations of returning to normal health consistently decreased (p = 0.009). CONCLUSION: Patients undergoing treatment for PJI experience significant psychological burden, with implications for quality of life and expectations of recovery. The findings underscore the importance of addressing psychological well-being in the management of PJI and emphasize the need for comprehensive care strategies that encompass both somatic and psychological dimensions.

Effect of functional relaxation on the quality of life in patients with periprosthetic joint infection: Protocol for a randomised controlled trial.

INTRODUCTION: Periprosthetic joint infection (PJI) is a devastating complication in orthopaedic and trauma surgery, which puts a high burden on the patients involving recurrent hospitalisation, prolonged courses of antibiotic medication, severe pain and long periods of immobility as well as high levels of psychological distress. Thus, this multicentre study aims at implementing body-oriented psychotherapy in clinical practice and evaluating its therapeutic effect on the quality of life. METHODS AND ANALYSIS: A prospective, parallel two-armed randomised controlled trial with approximately n=270 patients with verified PJI treated surgically with a one-staged exchange, or a two-staged exchange will be conducted. Functional relaxation (FR) therapy will be implemented as a group therapy. FR originally belongs to the psychodynamically based body-oriented psychotherapy. Intervention techniques consist of minute movements of small joints, which are performed during relaxed expiration accompanied by an exploration of differences of body feelings. A group will include 3-8 patients, led by a specialist physiotherapist certified in FR once a week. The participants are consecutively admitted to the class and participate in 12 sessions. The control group will consist of patients receiving an unspecific 'placebo relaxation' intervention for the same duration. The primary efficacy endpoint is the mental component summary and physical component summary of quality of life assessed by the 36-Item Short Form Health Survey (SF-36) after 6 months. Secondary outcomes include SF-36 scores after 12 months, consumption of pain medication, mobility measured by the Parker mobility score and the physical activity measured by daily steps with an accelerometer (actibelt). ETHICS AND DISSEMINATION: Approval from the Ethical Committee of the University Hospital Regensburg was received (file number: 21-2226-101). Written, informed consent to participate will be obtained from all participants. Results will be made available in the form of peer-reviewed publications and presentation in congresses. TRIAL REGISTRATION NUMBER: DRKS00028881; German Clinical Trials Register.

Low Adherence to Pneumococcal Vaccination in Lung Cancer Patients in a Tertiary Care University Hospital in Southern Germany.

INTRODUCTION: The aim of this study was to investigate the adherence to vaccinations, especially pneumococcal vaccinations, in lung cancer patients. METHODS: the study was performed at the University Hospital Regensburg, Germany. All patients with a regular appointment scheduled between 1 December 2020 and 29 April 2021 and who provided informed consent were included. Available medical records, vaccination certificates, and a questionnaire were analyzed. RESULTS: we included 136 lung cancer patients (NSCLC n = 113, 83.1%, SCLC n = 23, 16.9%). A correct pneumococcal vaccination according to national recommendations was performed in 9.4% (12/127) of the patients. A correct vaccination was performed for tetanus in 50.4% (66/131), diphtheria in 34.4% (44/128), poliomyelitis in 25.8% (33/128), tick-borne encephalitis in 40.7% (24/59), hepatitis A in 45.5% (7/11), hepatitis B in 38.5% (5/13), shingles in 3.0% (3/101), measles in 50.0% (3/6), pertussis in 47.7% (62/130), influenza in 54.4% (74/136), and meningococcal meningitis in 0% (0/2) of the patients. CONCLUSION: adherence to pneumococcal vaccinations, as well as to other vaccinations, is low in lung cancer patients.

L-leucine improves anemia and growth in patients with transfusion-dependent Diamond-Blackfan anemia: Results from a multicenter pilot phase I/II study from the Diamond-Blackfan Anemia Registry.

BACKGROUND: Diamond-Blackfan anemia (DBA) is an inherited bone marrow failure syndrome characterized by anemia, short stature, congenital anomalies, and cancer predisposition. Most cases are due to mutations in genes encoding ribosomal proteins (RP) leading to RP haploinsufficiency. Effective treatments for the anemia of DBA include chronic red cell transfusions, long-term corticosteroid therapy, or hematopoietic stem cell transplantation. In a small patient series and in animal models, there have been hematologic responses to L-leucine with amelioration of anemia. The study objectives of this clinical trial were to determine feasibility, safety, and efficacy of L-leucine in transfusion-dependent patients with DBA. PROCEDURE: Patients ≥2 years of age received L-leucine 700 mg/m2 orally three times daily for nine months to determine a hematologic response and any improvement in growth (NCT01362595). RESULTS: This multicenter, phase I/II study enrolled 55 subjects; 43 were evaluable. There were 21 males; the median age at enrollment was 10.4 years (range, 2.5-46.1 years). No significant adverse events were attributable to L-leucine. Two subjects had a complete erythroid response and five had a partial response. Nine of 25, and 11 of 25, subjects experienced a positive weight and height percentile change, respectively, at the end of therapy. CONCLUSIONS: L-leucine is safe, resulted in an erythroid response in 16% of subjects with DBA, and led to an increase in weight and linear growth velocity in 36% and 44% of evaluable subjects, respectively. Further studies will be critical to understand the role of L-leucine in the management of patients with DBA.

Favorable survival maintained in children who have myeloid leukemia associated with Down syndrome using reduced-dose chemotherapy on Children's Oncology Group trial A2971: a report from the Children's Oncology Group.

BACKGROUND: Children who are treated for myeloid leukemia associated with Down syndrome (DS) experience superior survival compared with children who have myeloid leukemia without DS. To maintain excellent outcomes while avoiding toxicity, the Children's Oncology Group (COG) conducted the phase 3 trial COG A2971, the first trial solely designed to provide uniform treatment of myeloid leukemia in North American children with DS. A2971 eliminated 2 induction drugs and 3 months of maintenance therapy from the standard-timing regimen of dexamethasone, cytarabine, 6-thioguanine, etoposide, and rubidomycin/daunomycin (DCTER) used in the previous study (Children's Cancer Group [CCG] 2891). METHODS: COG A2971 was a multi-institutional, nonrandomized, clinical trial that enrolled 132 patients who had DS with either acute myeloid leukemia (n = 91) or myelodysplastic syndrome (n = 41). RESULTS: The median follow-up was 4.8 years (range, 0.8-8.6 years), the median age at diagnosis was 1.7 years (range, 0.3-13.6 years), and the median white blood cell count was 6200/µL (range, 900-164,900/µL). The remission rate (92.7% ± 6%) was similar to that reported in the CCG 2891 study (91.3% ± 5%; P = .679). The 5-year event free survival (EFS) rate was 79% ± 7% (vs 77% ± 7% in CCG 2891; P = .589), the disease-free survival (DFS) rate was 89% ± 6% (vs 85% ± 6% in CCG 2891; P = .337), and the overall survival rate was 84% ± 6% (vs 79% ± 7% in CCG 2891; P = .302). Induction day-14 bone marrow response trended toward a more favorable outcome (EFS: P = .12). Age >4 years was an adverse risk factor (5-year EFS rate: 33% ± 38% for children aged >4 years [median, 8.5 years; n = 6] vs 81% ± 7% for children ages 0-4 years [median, 1.7 years; n = 126]; P = .001). CONCLUSIONS: The COG A2971 trial reduced the chemotherapy dose and maintained survival to that achieved by the CCG 2891 trial in children who had myeloid leukemia associated with DS.

Natural history of transient myeloproliferative disorder clinically diagnosed in Down syndrome neonates: a report from the Children's Oncology Group Study A2971.

Transient myeloproliferative disorder (TMD), restricted to newborns with trisomy 21, is a megakaryocytic leukemia that although lethal in some is distinguished by its spontaneous resolution. Later development of acute myeloid leukemia (AML) occurs in some. Prospective enrollment (n = 135) elucidated the natural history in Down syndrome (DS) patients diagnosed with TMD via the use of uniform monitoring and intervention guidelines. Prevalent at diagnosis were leukocytosis, peripheral blast exceeding marrow blast percentage, and hepatomegaly. Among those with life-threatening symptoms, most (n = 29/38; 76%) received intervention therapy until symptoms abated and then were monitored similarly. Organomegaly with cardiopulmonary compromise most frequently led to intervention (43%). Death occurred in 21% but only 10% were attributable to TMD (intervention vs observation patients: 13/14 vs 1/15 because of TMD). Among those solely observed, peripheral blasts and all other TMD symptoms cleared at a median of 36 and 49 days from diagnosis, respectively. On the basis of the diagnostic clinical findings of hepatomegaly with or without life-threatening symptoms, 3 groups were identified with differing survival: low risk with neither finding (38%), intermediate risk with hepatomegaly alone (40%), and high risk with both (21%; overall survival: 92% ± 8%, 77% ± 12%, and 51% ± 19%, respectively; P ≤ .001). Among all, AML subsequently occurred in 16% at a median of 441 days (range, 118-1085 days). The trial is registered at http://www.clinicaltrials.gov as NCT00003593.

[Development of a novel device for adaptive testing according to ICD-10: PsyPAM--psychosomatic physician-patient module]. / Entwicklung eines neuen Instruments zur adaptierten Diagnostik psychischer Störungen nach ICD-10: PsyPAM - Psychosomatisches Patienten-Arzt-Modul.

OBJECTIVES: There is a high demand for efficient and time-saving diagnostic procedures. The paper deals with the development and first clinical testing of a computerized diagnostic system, facilitating adaptive testing. METHODS: For diagnostic of the most common disorders, in accordance with Chapter F of the ICD-10, a psychosomatic physician-patient module (PsyPAM) was developed, which is a partially standardized, computerized interview procedure. In a pilot study the diagnostic results achieved with the PsyPAM-system were compared with clinical diagnoses, according with ICD-10 in n=115 patients. RESULTS: About 88% of clinical diagnoses used as a reference base were also established by the PsyPAM-system. The average total processing time for PsyPAM-diagnostics was 22.3 min. CONCLUSIONS: The PsyPAM-system is a promising and user-friendly screening tool with a short processing time, and is well worth further development and testing in daily clinical practice.

Sustained, long-term renal stabilization after 54 months of agalsidase beta therapy in patients with Fabry disease.

Fabry disease, an inherited deficiency of the lysosomal enzyme alpha-galactosidase A, causes progressive intralysosomal accumulation of globotriaosylceramide (GL-3) and premature death from renal, cardiac, and cerebrovascular manifestations. To determine the long-term safety and efficacy of recombinant human alpha-galactosidase A, an open-label, phase III extension study was conducted, involving 58 patients who had classic Fabry disease and completed a 20-wk, double-blind, randomized, placebo-controlled, phase III study of agalsidase beta and were transitioned to an extension trial to receive biweekly 1 mg/kg agalsidase beta for up to an additional 54 mo. GL-3 accumulation was evaluated in the capillary endothelia of the skin, kidney, and heart. Renal function was assessed. By month 54, all patients with optional kidney biopsies (n = 8) maintained complete GL-3 clearance in renal capillary endothelial cells and multiple cell types. Continued, complete clearance of skin (31 of 36) and heart (six of eight) capillary endothelium was demonstrated. Mean plasma GL-3 levels remained decreased in the normal range. Median serum creatinine and estimated GFR remained stable (normal) in patients with renal data at month 54 (n = 41). Six patients had renal disease progression; most (four of six) were older than 40 yr and had significant proteinuria at baseline and evidence of sclerotic glomeruli pretreatment. Adverse events were generally mild and unrelated to treatment. The most common treatment-related adverse events were infusion-associated reactions, which decreased over time. Long-term agalsidase beta therapy stabilizes renal function in patients without renal involvement at baseline, maintains reduction of plasma GL-3, and sustains GL-3 clearance in capillary endothelial cells and multiple renal cell types.

Pharmacokinetic evaluation of darbepoetin alfa for the treatment of pediatric patients with chemotherapy-induced anemia.

BACKGROUND: Cancer patients undergoing chemotherapy often develop anemia, which can increase the risk for transfusions and fatigue. The recombinant erythropoiesis-stimulating agent darbepoetin alfa can effectively treat chemotherapy-induced anemia (CIA) in adults, but limited data are available regarding its use in pediatric cancer patients. The goals of this phase 1, open-label, uncontrolled study were to assess the pharmacokinetic profile and safety of darbepoetin alfa in pediatric patients with CIA. PROCEDURE: Pediatric patients with nonmyeloid malignancies and CIA received up to six doses of darbepoetin alfa 2.25 mcg/kg subcutaneously. After the first dose, the pharmacokinetic properties of darbepoetin alfa were assessed during a 14-day sampling period. All subsequent doses were given weekly with predose blood samples collected before study drug administration. RESULTS: After a single dose of darbepoetin alfa, the mean (SD) peak serum concentration was 10.5 (3) ng/ml, and the median time to peak concentration was 71.4 hr. Darbepoetin alfa exhibited a mean (SD) terminal half-life of 49.4 (32) hr. Upon repeated weekly administration, no evidence of darbepoetin alfa accumulation was observed though there was high intra- and inter-individual variability. In addition, darbepoetin alfa was well tolerated; some study patients experienced increases in hemoglobin. CONCLUSIONS: The pharmacokinetic profile of darbepoetin alfa indicated that it was slowly absorbed and exhibited a long terminal half-life in these pediatric study patients with CIA.

[Implementation of the multi-center basis documentation CL-BaDo for conciliar and liaison services: generating data for internal quality management and cost calculation]. / Implementierung der multizentrischen Basisdokumentation CL-BaDo für den Konsiliarund Liaisondienst: Generierung von Daten für internes Qualitätsmanagement und Kostenkalkulation.

In the German DRG system the funding of CL services is not ensured. The documentation of psychiatric comorbidity and CL care delivery is a pre-condition to the development of funding models for CL-services. A task force of several German psychosomatic associations (German College of Psychosomatic Medicine, German Society of Psychosomatic Medicine and Psychotherapy, General Medical Society for Psychotherapy) developed a new documentation form for CL-services (CL-BaDo). The pilot study explored the multicenter implementation of CL-BaDo and the use of the documentation form for quality management and cost calculation. Over a period of at least three months, participating CL-services documented all CL cases consecutively with the CL-BaDo. One site applied full electronic data processing. 2116 CL cases from eight psychosomatic CL-services were analysed. The CL-BaDo is a time-efficient, feasible and acceptable documentation form for CL-service delivery. The full electronic data processing enables networking with a hospital information system to produce higher data quality. The data of CL-BaDo can be used locally for quality management, development of management strategies and communication with consultants, as well as nationwide for health policy questions and research.

Medical decision-making of the patient in the context of the family: results of a survey.

GOALS OF THE STUDY: From the perspective of patient autonomy, the family is often looked upon as a troublemaker in medical decision-making. The question remains open as to whether it is possible to do justice to the autonomy of the individual patient and to the claims of his family at the same time. PATIENTS AND METHODS: A clinical study was undertaken when both patients and dependents were interviewed. One hundred people (50 pairs) participated in this study and could be analyzed. A questionnaire consisting of 15 items was used and was evaluated to see if and how the attitudes concerning medical decision-making differ between patient and dependent. RESULTS: The majority of the interviewees (89%) agreed with the opinion that medical decisions should be made jointly by the patient, the family, and the doctor. Ninety-three percent approved of the claim to inform not only the patient, but also the family. Seventy percent of the patients and 54% of the dependents think that the family is entitled to have a say in matters concerning medical decision-making, only 30% of the patients, but 42% of the dependents argued against this view. Eighty-four percent of the patients argued against a change in this right at the end of life, which was approved by 32% of the family members. CONCLUSIONS: The family plays a central role in medical decision-making. This could be shown by a survey among patients with malignant diseases and their dependents. These initial findings must be verified in a larger population. The increased inclusion of the family in the process of medical decision-making corresponds in general to the expressed will of the patients. The model of shared decision-making is favored by values which both the family and the patient have in common. Thus, a family-based decision-making theory needs to be formulated in the future.

[Self-help and consultation via Internet. Self-responsible users redefine the physician-patient relationship]. / Selbsthilfe und Beratung im Internet. Mündige Benutzer können die Arzt-Patienten-Beziehung neu gestalten.

Using e-health portals to the internet seeking information about one's illness and to exchange experience with other sick persons can result in more self-responsible patients and in a more partnership-based physician-patient relationship. Especially with serious and chronic diseases like cancer, HIV infection, eating disorders, and depression, concerned patients may find support by accessing web pages and by using internet communication like message boards, mailing lists, and chat rooms. In an online questionnaire, internet users with eating disorders stated that they felt understood by their internet peers and, therefore, were encouraged to start therapy. Physicians may fear their advance in knowledge to decrease, resulting in an overprotective attitude to the informed patient. Nevertheless, they will recognize, by active participation, that the medical internet may promote an earlier start of expert-guided therapy, improved compliance, aftercare, and basic care independent of place and time. However, further evaluation of internet-supported treatment is required.

Chronic fatigue and indicators of long-term employment disability in psychosomatic inpatients.

The major goal of this study was to determine indictors of long-term disability for psychosomatic inpatients with chronic fatigue syndrome. To this end, a cross-sectional study was performed with a random sample of patients (n=1000, response rate: 83.9%) at a psychosomatic inpatient clinic. 51.1% of the patients (n=429) reported intensely persistent exhaustion that had no logical relation to actual exertion. 159 (37.1%) patients in this group were disabled from working and these comprised the main target group of this study. Significantly more patients in the target group worked part time, were disabled for a disproportionately long period of time (50.9% of all were disabled for more than 6 months in the previous year), and felt stressed because of conflicts with their superiors and/or colleagues (in each case, P<0.01). While more frequent psychological comorbidity was not found, they reported physical complaints more often. It was not the patients fit for work who felt more burdened with chronic fatigue, but rather the employment-disabled, who were actually exposed to fewer demands. These patients had, in comparison with those fit to work, a stronger fixation on somatic complaints, inadequate perception of physical and psychic sensations, difficulties getting along with other people and in coping with a regular job (in each case, P<0.01). Prospective examination of these indicators could help detect predictor variables for long-term disability in chronic fatigue. Such predictors could contribute to timely social-medical assessment and treatment.

Protracted radiotherapy treatment duration in medulloblastoma.

From 1970 to 1997, 63 patients with medulloblastoma were treated with craniospinal irradiation followed by a posterior fossa boost. There were 38 males and 25 females with a median age of 9 years (range, 8 months to 53 years). Stage was T1-T3a in 50 (79%) and M0 in 38 patients (60%) according to the Chang staging system. Gross total resection of the primary tumor was achieved in 33 (52%) and median posterior fossa dose was 54 Gy, with 55 (87%) receiving > or =50 Gy. Median radiotherapy treatment duration was 49 days (range, 30-104 days) with 35 patients (56%) completing radiotherapy in <50 days. The most common reasons for a protracted radiotherapy treatment duration > or =50 days were hematologic toxicity (46%) and use of <1.6 Gy fraction size per day (29%). Chemotherapy was used in 22 (35%). Median follow-up time was 10.8 years (range, 2-28.5 years). The 5- and 10-year freedom from progression rates were 58% +/- 13% and 50% +/- 13%, respectively, whereas the 5- and 10-year posterior fossa control rates were 61% +/- 12% and 54% +/- 13%, respectively. On multivariate analysis, age > or =3 years, M0 status, > or =50 Gy PFB dose, radiotherapy treatment duration <50 days, and use of chemotherapy correlated with better freedom from progression and posterior fossa control rates. The 5- and 10-year freedom from progression rates were 67% +/- 15% and 64% +/- 16%, respectively, for patients with radiotherapy treatment duration <50 days and were 42% +/- 20% and 29% +/- 18%, respectively, for duration > or =50 days ( p= 0.0026, log-rank test). The 5- and 10-year posterior fossa control rates were 70% +/- 15% and 70% +/- 15%, respectively, for radiotherapy treatment duration <50 days and 46% +/- 20% and 33% +/- 19%, respectively, for duration > or =50 days ( p= 0.0037, log-rank test). In addition to age > or =3 years, M0 stage, use of adjuvant chemotherapy, and posterior fossa dose > or =50 Gy, our findings also reveal that radiotherapy treatment duration <50 days has a favorable prognostic outcome in patients with medulloblastoma.

Aberrant T-cell antigen receptor-mediated responses in autoimmune lymphoproliferative syndrome.

Autoimmune Lymphoproliferative Syndrome (ALPS) is a disorder of defective lymphocyte apoptosis due to mutations of the Fas receptor and other molecules in the Fas signaling pathway. In addition to accumulation of CD4(-) CD8(-) double-negative (DN) T cells, many patients display a dysregulated cytokine pattern with dysfunctional T cells, suggesting Fas defects may impact pathways of T-cell activation/differentiation. Here, we report two novel mutations in the Fas receptor resulting in an ALPS phenotype. Utilizing flow cytometry, we found anti-CD3 activated CD4(+) T cells from these patients were incapable of fully upregulating activation markers (CD25, CD69, and CD40L) or producing interferon-gamma and IL-2. Additionally, DN T cells were unable to transduce proximal T-cell antigen receptor signals or produce cytokines. Furthermore, DN T cells overexpressed CD57 and phenotypically resembled end-stage effector cells. As DN T cells were essentially anergic, the clinical manifestations of autoimmunity are more likely to be a consequence of aberrant cytokine secretion within the CD4(+) T-cell subpopulation.