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PubMed2006

Thrombolysis for acute lower limb ischaemia--a prospective, randomised, multicentre study comparing two strategies.

OBJECTIVES: To test if initial high-dose, pulse-spray thrombolysis improves the early and late outcome of lower limb ischaemia as compared with low-dose infusion alone. DESIGN: Prospective randomised multicentre study. MATERIAL AND METHODS: Patients with acute and sub-acute (<30 days) lower limb ischaemia were randomised following angiography. Group 1 (n=58) received pulse-spray infusion of recombinant plasminogen activator (rt-PA, 15 mg/h) for 2h followed by low-dose infusion if needed. Group 2 (n=63) were only treated with low-dose infusion (0.5mg/h) of rt-PA for 48 h. Underlying lesions were corrected if required. RESULTS: The study was stopped prematurely. Complications were equally frequent in both groups. More than 75% lysis was accomplished in 78 versus 67% of the patients (p=0.21). Primary endpoints (re-occlusion, incomplete lysis, life-threatening complication, amputation, or death) were reached in 24 versus 32% of the patients (p=0.35). Neither vascular patency nor clinical parameters differed during the first year, but re-interventions tended to be more frequent (p=0.040 at 1 month; p=0.090 at 1 year) and of a greater magnitude (p=0.028) in group 2. CONCLUSIONS: There was no obvious advantage with initial high-dose thrombolysis, which may be a type-2 error. A reduction of major re-interventions was recorded.

Aged↗

PubMed2003

Adjunctive therapy versus alternative monotherapy in patients with partial epilepsy failing on a single drug: a multicentre, randomised, pragmatic controlled trial.

OBJECTIVE: To evaluate the value of alternative monotherapy versus adjunctive therapy in partial epilepsy refractory to single antiepileptic drug (AED) therapy. DESIGN AND METHODS: In a multicentre, parallel-group, open-label study, patients with cryptogenic or symptomatic partial epilepsy not controlled after single or sequential AED monotherapies were randomised to monotherapy with an alternative AED or to adjunctive therapy with a second AED. The AED to be added/substituted and dose adjustments were determined by the physician's best judgement. Patients were followed up until withdrawal from the allocated treatment or for 12 months, whichever first. Outcome measures included proportion of patients continuing on the assigned treatment strategy, proportion of patients seizure-free after achieving the target maintenance dose, and adverse effects rates. Data were analysed by actuarial life tables, Kaplan-Meier survival analysis and Cox proportional hazard regression model. RESULTS: Of a total of 157 patients (including 94 previously exposed to only one AED), 76 were randomised to alternative monotherapy and 81 to adjunctive therapy. The two groups were balanced in clinical characteristics. The 12-month cumulative probability of remaining on the assigned treatment was 55% in patients randomised to alternative monotherapy and 65% in those randomised to adjunctive therapy (P=0.74). The 12-month probability of remaining seizure-free was 14 and 16%, respectively (P=0.74). Adverse effects were similar in the two groups. No significant differences in outcome within or between groups were identified based on etiology of epilepsy and previous AED exposure. CONCLUSIONS: Although these findings should be interpreted with caution due to the low statistical power resulting from the relatively small sample size, alternative monotherapy and adjunctive therapy were associated with similar outcomes. Further work is required to determine whether outcome could be improved through identification of specific AED combinations with synergistic activity.

Adolescent↗

PubMed2004

Frequency, clinical presentation and evolution of renal oncocytomas: multicentric experience from a European database.

OBJECTIVES: To understand the clinical behavior of renal oncocytoma in a retrospective analysis of a European multicentric nephrectomies database. METHODS: The records of 891 patients who underwent surgical resection of renal neoplasm were reviewed. Relevant clinical and pathological data for each patient were retrieved in a database. RESULTS: Thirty-two (3.6%) cases of renal oncocytoma were identified. Twenty patients (62.5%) were asymptomatic. No case of lymphatic invasion or metastatic disease, nor any evidence of vascular or fat tissue invasion was found. Thirty-one cases (96%) exhibited low mitotic activity. In one case the presence of renal clear cell carcinoma (diameter: 1.5cm) was found. After a median follow-up of 42 months, 87.5% of patients were alive with no evidence of tumor, while 9.3% of patients had died for non-malignant causes. One patient had not treated the tumor surgically and was disease-free at a 27-month follow-up. CONCLUSIONS: Renal oncocytoma is a benign neoplasm, characterized by slow growth and excellent prognosis after surgery. Nephron sparing techniques may be adequate for tumor removal.

Adenocarcinoma, Clear Cell↗

PubMed2004

Surgical treatment of female stress urinary incontinence with a trans-obturator-tape (T.O.T.) Uratape: short term results of a prospective multicentric study.

OBJECTIVE: The aim of the study was to assess the efficacy and safety of a new minimally invasive surgical procedure using the Trans-Obturator-Tape Uratape to treat female stress urinary incontinence. PATIENTS AND METHODS: 183 women with stress urinary incontinence (SUI) associated with urethral hypermobility, underwent the T.O.T. procedure (October 2001 to March 2003). 26 patients were previously operated for incontinence. 26 patients were operated at the same time for their genital prolapse. Mean age was 56 years (29-87). 50/183 patients were having mixed incontinence. A non-elastic, polypropylene tape (UraTape, Mentor-Porgès) with a silicon coated central part was placed under the mid-urethra. The surgical placement technique utilises a trans-obturator percutaneous approach. All patients underwent post-operative clinical examination, cough-stress test (full bladder), uroflowmetry, and post-voiding residual assessment. RESULTS: Mean follow-up was 7 months (1-21). At 1 year follow-up 80.5% of the patients were completely cured and 7.5% were improved. The overall peri-operative complication rate was 2.2% with no vascular, nerve or bowel injury. 6 patients (3.3%) had post-operative urinary retention. CONCLUSION: The present multicentric study confirms the results obtained by the instigator of the technique, E. Delorme, and allows us to consider T.O.T. as an effective and safe technique for the treatment of female stress urinary incontinence, alone or in combination with prolapse repair.

Adult↗

PubMed2005

Peri-operative complications and pain after the suburethral sling procedure for urinary stress incontinence: a French prospective randomised multicentre study comparing the retropubic and transobturator routes.

OBJECTIVE: To compare peri-operative complications, pain, and the immediate functional results of the sub-urethral sling procedure for urinary stress incontinence by the retropublic and transobturator routes, using a non-elastic polypropylene sub-urethral sling. PATIENTS AND METHODS: This prospective, multicentre study involved 88 women undergoing the sub-urethral sling procedure for stress urinary incontinence (SUI). The retropubic route (RPR) and the transobturator route (TOR) were used in respectively 42 and 46 cases. The characteristics of the women in the RPR and TOR groups were as follows: mean age (+/-standard deviation) 56.8+/-12 years and 53.4+/-10 years, respectively; mean BMI: 25+/-4 and 26+/-4; mean parity: 2.1+/-0.9 and 2+/-1 children; post-menopausal status: 66.7% and 58.7%; prior surgery for SUI: 7.1% and 6.5%; and prior hysterectomy: 21.4% and 26.1%. None of these characteristics differed significantly between the groups. Likewise, pre-operative urinary functional status (SUI stage, and pollakiuria, nocturia and urgency rates) was similar in the two groups. RESULTS: Mean hospital stay and overall morbidity rate were not significantly different between the RPR and TOR groups. Mean operating time was longer in the RPR group. Bladder injury was significantly more frequent in the RPR group and vaginal injury was significantly more frequent in the TOR group. Pain scores were significantly lower in the TOR group. The objective functional results at one month did not differ between the groups. Quality of life, evaluated with questionnaires and numerical rating scales, was similarly improved in the two groups. DISCUSSION: The suburethral sling procedure was less painful by the TOR route than by the RPR route. Bladder injury, haematomas and abscesses were only observed in the RPR group, while vaginal injury only occurred in the TOR group. The immediate functional results of the two approaches were similar.

Adult↗

PubMed2006

Functional results after the suburethral sling procedure for urinary stress incontinence: a prospective randomized multicentre study comparing the retropubic and transobturator routes.

OBJECTIVES: To compare short-term functional outcomes, urodynamic parameters, and quality of life of transobturator and retropubic routes in the cure of urinary stress incontinence. POPULATION AND METHODS: This prospective, multicentre study involved 88 women undergoing suburethral sling procedure for stress urinary incontinence (SUI). The retropubic route (RPR) and the transobturator route (TOR) were used in 42 and 46 women, respectively. No difference in epidemiologic and preoperative urinary functional status (SUI stage, and pollakiuria, nocturia, and urgency rates) was found between the groups. Functional results and quality of life were evaluated before surgery and at 1, 3, 6, and 12 mo postoperatively. Urodynamic examinations were performed before and 3 mo after surgery. RESULTS: The mean follow-up was 10 mo. No difference in the rate of de novo urge incontinence and immediate and late voiding dysfunction was noted between the groups. No difference in the cure rate was observed between the groups (89.3% in the RPR group and 88.6% in the TOR group). RPR was associated with a significant decrease in maximum urinary flow and an increase in residual urine volume. Quality of life was significantly improved after surgery without difference between the groups. CONCLUSIONS: Retropubic and transobturator routes for treatment of female SUI have similar high cure rates and quality of life improvement. Because of advantages in the rate of complications and postoperative pain previously demonstrated on the same population, the transobturator route appears to be the best option for the treatment of urinary incontinence.

Female↗

PubMed2026

Prevalence of homologous recombination repair genes alterations in metastatic castration-resistant prostate cancer, a multicentric study.

INTRODUCTION: Homologous Recombination Repair (HRR) genes alterations are a resistance mechanism to therapies by taxanes or Androgen Receptor Signalling inhibitors in Metastatic Castration Resistant Prostate Cancer (mCRPC). BRCA-mutated mCRPC patients are eligible to poly adenosine diphosphateribose polymerase inhibitors (PARPi). Therefore, assessing the population-specific prevalence of HRR-related genes alterations is of public healthcare importance. METHODS: This retrospective, non-interventional, multicentric study was conducted across 6 reference French centers in a "real-life" setting. 788 paraffin-embedded mCRPC patient-samples were included and submitted to testing for BRCA1/2 in six different centers; additionally, non-BRCA HRR-related genes were investigated in two different centers. RESULTS: Among the samples, n=602 (76.4%) were contributive for molecular testing. In multivariate analysis by logistic regression and sensitivity analysis, only sample age (P<0.01), sample surface area (P=0.02) and institution (P=0.018) remained statistically significant. BRCA alterations were detected in n=39/602 (6.5%) of contributive samples, with n=35 and n=4 alterations of BRCA2 and BRCA1 respectively. Non-BRCA HRR-related genes alterations were detected in n=12/157 (7.6%) of contributive samples, with alterations of mainly ATM (n=6, 3.8%), CDK12 (n=4, 2.5%) and CHEK2 (n=2, 1.3%). DISCUSSION: In this study, testing contributivity was similar or higher that of other studies in the literature, and observed mutations prevalences were similar to that of other screenings of western populations. Harmonising per-centres protocols and enhancing molecular testing contributivity with the screening of circulating DNA samples and expanding its range by including non-BRCA HRR-related genes in all reference centres will enable more patients to be accurately treated by targeted therapies. LEVEL OF EVIDENCE: 3 (grade C).

Male↗

PubMed2004

Preoperative assessment of multicentric occurrence in synchronous small and multiple hepatocellular carcinoma based on image-patterns and histological grading of non-cancerous region.

Recent studies have shown that the prognosis of patients with multicentric occurrence (MO) of hepatocellullar carcinoma (HCC) after curative resection, whether synchronous or metachronous, is significantly better than that of patients with intrahepatic metastasis (IM). We attempted to elucidate a group with high probability of MO of HCC by comparing the preoperative ultrasonography (US), computed tomography during arterial portography (CTAP) and CT arteriography (CTA) images with the histological grading of the non-cancerous region of the liver. The imaging and pathological characteristics of 97 nodules in 45 patients diagnosed as having small (<5cm) and oligonodular HCCs preoperatively were investigated. Histological diagnoses were as follows: 18 MO, 23 IM, and 4 unclassified (HCC with benign nodule). Histological grade of the liver tissue was assessed using the hepatitis activity index (HAI) score. No significant differences in tumor location and the mean size of co- or daughter nodules were noticed between the MO and IM patients. Of the 38 nodules in the MO patients, 20 were diagnosed as hyperechoic lesions on US, 20 as negative enhanced lesions on CTA and 12 as having positive portal flow on CTAP. A comparison of image-patterns between the synchronous nodules revealed that the MO group showed different images in at least one imaging technique, whereas in most IM patients similar images were produced by two or three imaging techniques. Moreover, all MO patients had an [Formula: see text], although more than half the IM patients had an [Formula: see text]. In patients with small and oligonodular HCCs, the nodules are highly likely to display MO, when showing both 1 or more different image patterns among US, CTA and CTAP and severe hepatitis such as HAI score >/=8.

Journal Article↗

PubMed2005

Patients' assessments of the effectiveness of homeopathic care in Norway: a prospective observational multicentre outcome study.

OBJECTIVE: To evaluate the patient reported effects of homeopathic care 6 months after first consultations. METHODS: Prospective uncontrolled observational multicentre outcome study. All patients visiting 80 homeopaths all over Norway for the first time in eight different time periods from 1996 to 1998 were approached. Patients wrote down their main complaint and scored its impact on daily living on a 100 mm Visual Analogue Scale (VAS) at the first consultation. Six months later they were asked to score again. The homeopaths recorded treatments given for up to two follow-up consultations. MAIN OUTCOME MEASURE: Predefined as a reduction of at least 10 mm in the VAS score between the first consultation and follow-up. RESULT: Patients 1097 were recruited, 654 completed the follow-up questionnaire. The main complaint improved by at least 10mm on the VAS for 71% (95% confidence interval 67-74%) of patients. The average reduction was 32mm (95% CI 30-35 mm). Fifty-one per cent (95% CI 48-55%) of the patients had an improvement in their general well being of more than 10 mm. The mean reduction in the whole group was 14mm (95% CI 12-16 mm). The proportion of patients using conventional medication reduced from 39% to 16%. Regression analysis showed that lower age and higher baseline score were predictors of better outcome. CONCLUSION: In this study, seven out of ten patients visiting a Norwegian homeopath reported a meaningful improvement in their main complaint 6 months after the initial consultation.

Confidence Intervals↗

PubMed2006

Osteoclast differentiation and bone resorption in multicentric reticulohistiocytosis.

Multicentric reticulohistiocytosis (MR) is a systemic disease of unknown cause characterized by the presence of a heavy macrophage infiltrate in skin and synovial tissues and the development of an erosive polyarthritis. The synovial fluid in MR is known to contain numerous mononuclear cells. In this study, we have determined whether these cells contribute to joint destruction in MR by differentiating them into osteoclasts. Synovial fluid mononuclear cells were isolated from the knee joint of a 44-year-old male with MR. These cells were cultured with various combinations of macrophage-colony stimulating factor, receptor activator for nuclear factor kappaB ligand (RANKL), tumor necrosis factor alpha, interleukin-1alpha, osteoprotegerin, and zoledronate. Osteoclast differentiation was assessed by expression of tartrate-resistant acid phosphatase, vitronectin receptor, and the extent of lacunar resorption. Most MR synovial fluid mononuclear cells expressed a macrophage phenotype (CD14(+), CD68(+), HLA-DR(+), CD11b(+)). Extensive osteoclast formation and lacunar resorption were noted in macrophage-colony stimulating factor/RANKL-treated cell cultures. MR synovial fluid contained increased tumor necrosis factor alpha and decreased osteoprotegerin compared with osteoarthritis synovial fluid. Lacunar resorption was inhibited in cultures containing zoledronate. Pamidronate treatment of the patient also reduced the number of synovial fluid macrophages and resulted in less osteoclast formation and lacunar resorption. MR synovial fluid contains numerous macrophages that are capable of differentiating into osteoclasts by the RANKL signaling pathway. Inhibitors of osteoclast formation and resorption activity may be of use in preventing the severe joint destruction that commonly occurs in MR.

Adult↗

PubMed2005

Designed sound and music environment in postanaesthesia care units--a multicentre study of patients and staff.

A multicentre study in five postanaesthesia care units (PACUs) was performed to investigate patient and staff opinion of a specially designed music environment (DME), related to geographical location. Patients (325) and staff (91) described their opinion by means of a questionnaire-anonymously in the case of staff. Patients were not asked beforehand for permission to play music. Amongst patients 267 (83%) found the sound environment with DME pleasant or very pleasant, 26 (6%) found it unpleasant, whereas 32 (11%) answered "no opinion". The opinion of the patients did not differ significantly with geographical location. A strong correlation (P<0.05) between a positive attitude towards DME and degree of relaxation and satisfaction with stay was found. The staff had an equally positive attitude towards the DME; but theirs varied significantly with location. The opinion of the staff was more similar concerning the beneficial effect on working conditions and distress, but varied still significantly. The opinion of the staff had no demonstrable impact on that of the patients.

Attitude of Health Personnel↗

PubMed2004

PROTEKT 1999-2000: a multicentre study of the antibiotic susceptibility of respiratory tract pathogens in Hong Kong, Japan and South Korea.

A multicentre surveillance study performed in the Far East during 1999-2000 investigated the in vitro activity of >20 antibacterials against common respiratory pathogens. In Hong Kong, Japan, and South Korea, 57.1, 44.5 and 71.5% Streptococcus pneumoniae were penicillin-resistant and 71.4, 77.9 and 87.6% were erythromycin-resistant, respectively. Overall, >90% of penicillin-resistant strains were also macrolide-resistant. All strains were susceptible to telithromycin. Fluoroquinolone-resistant isolates in Japan (1.3%), Hong Kong (14.3%) and South Korea (2.9%) were mostly co-resistant to penicillin, macrolides and tetracycline. Beta-lactamase production by Haemophilus influenzae isolates was 8.5% in Japan, 17.1% in Hong Kong and 64.7% in strains from South Korea. A single (0.27%) BLNAR isolate was obtained in Japan. There was no fluoroquinolone resistance. Moraxella catarrhalis was inhibited by telithromycin at <or=0.5mg/l and remained susceptible to macrolides, fluoroquinolones and amoxicillin-clavulanate. Resistance to antibacterials, particularly penicillin and macrolides, has reached high but stable levels in the Far East and the presence of multiply-resistant pneumococci is well established.

Drug Resistance, Bacterial↗

PubMed2006

Discrepancy between antibiotics administered in acute exacerbations of chronic bronchitis and susceptibility of isolated pathogens in respiratory samples: multicentre study in the primary care setting.

A national multicentre prevalence study was undertaken to determine the bacterial strains associated with mild-to-moderate acute exacerbations of chronic bronchitis (AECB) in the primary care setting and the susceptibility of isolated pathogens to different antimicrobials usually prescribed to these patients. All samples were processed by a central reference laboratory. Microdilution tests were carried out to establish the minimum inhibitory concentration (MIC) of various antimicrobials. A double-disk test was performed to establish the macrolide resistance phenotype in Streptococcus pneumoniae. Tests to detect the presence of beta-lactamase in Haemophilus influenzae and Moraxella catarrhalis and polymerase chain reaction to detect the presence of ermB and mefA genes in S. pneumoniae isolates were also performed. A total of 1537 patients were included in the trial and 468 microorganisms were isolated from sputum samples, with the most frequent isolates being S. pneumoniae (34.8%), M. catarrhalis (23.9%) and H. influenzae (12.6%). Resistance rates of pneumococci were 47.2% for penicillin, 1.2% for amoxicillin, 34.3% for macrolides (87.5% of which showed high-level resistance), 13.6% for cefuroxime/axetil and 4.2% for levofloxacin. No bacterial isolates showed resistance to telithromycin. Empirical antibiotic treatment was prescribed to 98.3% of patients, including macrolides to 36.6%, amoxicillin with or without clavulanic acid to 32.3% and fluoroquinolones to 16.1%. In conclusion, S. pneumoniae was the most frequently isolated bacteria in patients with mild-to-moderate AECB. Despite the high rates of resistance of pneumococci to macrolides, they continue to be the most widely used antibiotics in primary care to treat AECB.

Adult↗

PubMed2006

Efficacy of intensified hyperfractionated and accelerated radiotherapy and concurrent chemotherapy with carboplatin and 5-fluorouracil: updated results of a randomized multicentric trial in advanced head-and-neck cancer.

PURPOSE: To prove an expected benefit of concurrent radiochemotherapy (RCT), a two-arm randomized multicentric study was performed. In a subgroup analysis the influence of pretherapeutical hemoglobin level (p-Hb) on survival under locoregional control (SLC) was tested. PATIENTS AND METHODS: The study included primarily untreated Stage III/IV (International Union Against Cancer [UICC]) oropharyngeal and hypopharyngeal carcinomas. Patients were randomized to receive either hyperfractionated (hf) and accelerated (acc) RCT with two cycles 5-fluorouracil (600 mg/m(2)/day) and carboplatin (70 mg/m(2)/day) on Days 1-5 and 29-33 or hf-acc radiotherapy (RT) alone. Total RT dose in both arms was 69.9 Gy in 38 days in concomitant boost technique. RESULTS: After a median follow-up time of 57 months, SLC is significantly better in RCT than in RT (p = 0.01), with median SLC of 17 months and 11 months, respectively. Also overall survival (OS) shows a benefit for RCT (p = 0.016), with a median survival of 23 months for RCT and 16 months for RT. However, the benefit in SLC and OS is not seen in hypopharyngeal carcinomas. In a multivariate analysis of oropharyngeal cancer patients, p-Hb levels lower than 12.7 g/dL resulted in lower SLC compared with higher p-Hb levels up to 13.8 g/dL. P-Hb levels >13.8 g/dL did not further improve SLC. CONCLUSIONS: Hyperfractionated-accelerated RCT is superior to hf-acc RT in oropharyngeal carcinomas. P-Hb levels >13.8 g/dL do not further improve SLC.

Adult↗

PubMed2005

The practice of out-lying patients is dangerous: a multicentre comparison study of nursing care provided for trauma patients.

Pressure for acute hospital beds is a national problem with many acute trauma patients being admitted to non-trauma wards. This prospective multicentre questionnaire study of 220 qualified trauma and non-trauma nurses aims to compare the quality of nursing care that trauma patients receive when admitted to trauma wards and non-trauma wards. The questions included the nursing management of common fractures and post-operative conditions. The completed questionnaires were scored and the results analysed. Hundred percent of the questionnaires were completed and returned. The trauma nurses conveyed the importance of ice (85%) and elevation (97%) in the initial management of limb fractures. This compares with ice (10%) and elevation (50%) on the outlying wards. Trauma nurses correctly monitor for potentially devastating post-operative complications and compartment syndrome 87% of the time compared with 42% on outlying wards. Spinal injuries are managed appropriately 88% of the time on trauma wards compared with 36% on outlying wards. Trauma patients receive better nursing care when admitted to a trauma ward and are nursed by trauma nurses. Many of the out-lying wards provide sub-optimal trauma nursing care and a few are positively dangerous. We suggest that trauma patients should not be nursed on outlying wards.

Acute Disease↗

PubMed2006

Analysis of clustered data in multicentre trauma studies.

INTRODUCTION: In order to design multicentre studies an estimate of the correlation of the observations within each centre is necessary. A standard measure of the correlation between observations within each centre is the Intraclass Correlation Coefficient (ICC). METHOD: We used the National Trauma Data Bank (NTDB). By 2004, 448 trauma centres (including 110 level I and 123 level II trauma centres) from 43 states and US territories contributed over 1.2 million records to the NTDB. Data of patients directly transported from the scene of injury to level I or II trauma centres were used to calculate the ICC of in-hospital trauma fatality and emergency department (ED) shock rate. RESULTS: The ICCs of ED shock and in-hospital fatality rate were 0.010 (95% confidence interval (CI): 0.003-0.018) and 0.039 (95% CI: 0.028-0.050), respectively. The ICC of shock in the ED was the highest for penetrating injuries (0.017, 95% CI: 0.003-0.032) and the lowest for women (0.008, 95% CI: 0.002-0.013) although the observed difference between men and women was not statistically significant. The ICC of trauma fatality was the highest for penetrating injuries (0.073, 95% CI: 0.047-0.098), and the lowest for blunt injuries (0.029, 95% CI: 0.020-0.037). DISCUSSION: Although the calculated ICCs might seem so small as to be ignored, the required sample size in studies with exclusively exposed or non-exposed clusters depends on the ICC and the average number of subjects within clusters. Therefore, investigators should be aware of the influence that these ICCs might have on sample size and power of their studies.

Adult↗

PubMed2005

Proliferating multicentric reticulohistiocytosis associated with papillary serous carcinoma of the endometrium.

Multicentric reticulohistiocytosis (MRH) is a rare histocytic disease characterized by destructive arthritis in association with classic skin findings. Although MRH is not strictly a paraneoplastic disease, one quarter of cases are malignancy related. We report a case of MRH with an initial remission followed by an acute exacerbation several years later heralding the clinical presentation of endometrial carcinoma. During this flareup a skin biopsy specimen revealed a diffuse dermal infiltrate composed of histiocytes with ground-glass cytoplasm and multiple atypical mitoses. Approximately 40% of the cells stained with the proliferation marker Ki-67. Treatment of endometrial carcinoma resulted in improvement of skin and joint symptoms, and a repeat biopsy specimen no longer demonstrated mitotic figures. These findings support a reactive and proliferative cause of MRH.

Aged↗

PubMed2026

Comparing trajectories of cognitive functioning in treatment-resistant and non-resistant depression: a multicentre linear mixed-effects analysis.

BACKGROUND: Impaired cognitive functioning is a severe symptom in major depressive disorder (MDD). Recent evidence suggests it may be a central characteristic in its treatment resistant form (TRD), potentially constituting a clinical marker for treatment resistance and a target amenable to intervention. To date, cognitive functioning in TRD remains poorly understood and longitudinal investigations are scarce. METHODS: This observational prospective cohort study, including 320 patients diagnosed with MDD from the multicentre PROMPT study, examined differences in cognitive functioning between 118 TRD and 202 non-TRD patients over a period of twelve weeks in a real-world setting, using linear mixed modelling. Patients that failed to respond to at least two prior antidepressants trials at baseline were classified as TRD. RESULTS: TRD patients showed significantly poorer baseline performances than non-TRD patients in attention/processing speed (β = -0.45; 95%CI[-0.70, -0.19]; FDR-p = 0.003) and verbal memory (β = -0.45; 95%CI[-0.72, -0.18]; FDR-p = 0.003). Significant time × group interactions were observed in motor speed and verbal fluency tasks. Post-hoc-analyses revealed stagnation in TRD patients and significant improvement in non-TRD patients. Across all other tasks improvement was observed in both groups, and random effects showed large heterogeneity between patients, indicating notable individual differences in cognitive performances. CONCLUSIONS: The results suggest distinct recovery patters between non-TRD and TRD patients, and diminished functioning in TRD patients at the domain level. However, intact and diminished performances likely occur in both groups, warranting further investigation of cognitive heterogeneity. These short-term findings highlight the need for more comprehensive longitudinal research on cognition in TRD.

Humans↗