Management of obstructive pathology of the salivary glands in elderly patients: a preliminary study.

BACKGROUND: Obstructive pathology is a benign condition of the salivary glands that can affect elderly and co-morbid people. Sialoendoscopy is a minimally invasive surgical procedure with a success rate comparable to standard sialoadenectomy and has the advantage that it can be performed under local anaesthesia. METHODS: This study aimed to assess sialoendoscopy benefits in elderly patients unfit for general anaesthesia. A group of elderly patients (aged 65 years or more) undergoing sialoendoscopy under local anaesthesia were evaluated. Age, co-morbidities, surgical time, hospital stay, and complication and recurrence rates were assessed. RESULTS: Nineteen sialoendoscopies were performed in 18 elderly patients with a mean age of 69.7 ± 5.6 years, with some of them suffering from multiple co-morbidities. Surgery was successful in 16 patients, while surgery was unsuccessful in 2 patients because of intraglandular stones. The average surgical duration was 54.5 ± 30.1 minutes, and all patients were discharged 2-3 hours after surgery. No post-operative complications were found and only one patient had recurrence during follow up. CONCLUSION: Sialoendoscopy under local anaesthesia is a safe and effective procedure in elderly patients who are more prone to complications.

Two-month stop in mammographic screening significantly impacts on breast cancer stage at diagnosis and upfront treatment in the COVID era.

INTRODUCTION: The present analysis aims to evaluate the consequences of a 2-month interruption of mammographic screening on breast cancer (BC) stage at diagnosis and upfront treatments in a region of Northern Italy highly affected by the severe acute respiratory syndrome-related coronavirus-2 (SARS-CoV-2) virus. METHODS: This retrospective single-institution analysis compared the clinical pathological characteristics of BC diagnosed between May 2020 and July 2020, after a 2-month screening interruption, with BC diagnosed in the same trimester of 2019 when mammographic screening was regularly carried out. RESULTS: The 2-month stop in mammographic screening produced a significant decrease in in situ BC diagnosis (-10.4%) and an increase in node-positive (+11.2%) and stage III BC (+10.3%). A major impact was on the subgroup of patients with BC at high proliferation rates. Among these, the rate of node-positive BC increased by 18.5% and stage III by 11.4%. In the subgroup of patients with low proliferation rates, a 9.3% increase in stage III tumors was observed, although node-positive tumors remained stable. Despite screening interruption, procedures to establish a definitive diagnosis and treatment start were subsequently carried out without delay. CONCLUSION: Our data showed an increase in node-positive and stage III BC after a 2-month stop in BC screening. These findings support recommendations for a quick restoration of BC screening at full capacity, with adequate prioritization strategies to mitigate harm and meet infection prevention requirements.

Autophagy mediates epithelial cancer chemoresistance by reducing p62/SQSTM1 accumulation.

To cope with intrinsic and environmental stress, cancer cells rely on adaptive pathways more than non-transformed counterparts. Such non-oncogene addiction offers new therapeutic targets and strategies to overcome chemoresistance. In an attempt to study the role of adaptive pathways in acquired drug resistance in carcinoma cells, we devised a model of in vitro conditioning to three standard chemotherapeutic agents, cisplatin, 5-fluorouracil, and docetaxel, from the epithelial cancer cell line, HEp-2, and investigated the mechanisms underlying reduced drug sensitivity. We found that triple-resistant cells suffered from higher levels of oxidative stress, and showed heightened anti-stress responses, including the antioxidant Nrf2 pathway and autophagy, a conserved pleiotropic homeostatic strategy, mediating the clearance of aggregates marked by the adapter p62/SQSTM1. As a result, re-administration of chemotherapeutic agents failed to induce further accumulation of reactive oxygen species and p62. Moreover, autophagy proved responsible for chemoresistance through the avoidance of p62 accumulation into toxic protein aggregates. Indeed, p62 ablation was sufficient to confer resistance in parental cells, and genetic and pharmacological autophagic inhibition restored drug sensitivity in resistant cells in a p62-dependent manner. Finally, exogenous expression of mutant p62 lacking the ubiquitin- and LC3-binding domains, required for autophagic engulfment, increased chemosensitivity in TDR HEp-2 cells. Altogether, these findings offer a cellular system to investigate the bases of acquired chemoresistance of epithelial cancers and encourage challenging the prognostic and antineoplastic therapeutic potential of p62 toxicity.

[A more and more painful intrauterine device where it is not enough to see the wires to exclude malposition!]. / Un stérilet qui fait de plus en plus mal où il ne suffit pas d'en voir les fils pour exclure une malposition !

We report a case of a 30-year-old woman with an intrauterine device (IUD) improperly inserted deep within the myometrium, with a muscularis layer injury of the recto-sigmoid colon resulting of a uterine perforation and presented as abdomino-pelvic pain and dyspareunia. The ultrasonographic control of the IUD after the insertion (performed seven months before) was not checked. Cervical examination showed the strings of the IUD. The ultrasonographic exploration identified an intra-myometrial IUD with fundus perforation of the uterus. A laparoscopic exploration permitting the removal of the IUD revealed an insertion through the bowel wall. The lessons to draw of about this case report are discussed through a brief review of the literature.

Genetics in health care: an overview of current and emerging models.

BACKGROUND: With advances in genetic and genomic medicine, the optimal integration of genetic services into the health care system remains of major concern in many countries. OBJECTIVES: To review the current organisation of genetic services, mostly in Europe, North America and Australia, explore emerging service delivery models, and probe challenges inherent in the transition process. METHODS: We conducted a literature review of genetics in clinical practice: testing, diagnosis, counselling, and treatment. We examined the basic structures of genetic services, examples of integrated networks, and existing professional resources. We investigated services belonging traditionally in medical genetics as well as those developed for more common diseases. RESULTS: Multidisciplinary specialist clinics and coordinated services appeared to be key to delivering proper care in rare genetic disorders. For oncogenetics, neurogenetics and cardiogenetics, interprofessional collaboration between geneticists and other specialists seemed to be favoured. On the other hand, there was also a tendency toward the integration of genetic services directly into primary care. Among the most pressing challenges was the morphing of paediatric care into adult care. CONCLUSION: The coordination of activities between professionals in first-, second-, and third-line medical care is a primary objective calling for the reconfiguration of professional roles and responsibilities. This entails the forging of new relationships as well as an enhanced sharing of expertise and genetic information, including information regarding services. Barriers to overcome include the redistribution of roles, sharing of data and databases, and the lack of preparedness of non-genetics professionals and of the health care system in general.

Physical and clinical comparison between a screen-film system and a dual-side reading mammography-dedicated computed radiography system.

BACKGROUND: Digital mammography systems, thanks to a physical performance better than conventional screen-film units, have the potential of reducing the dose to patients, without decreasing the diagnostic accuracy. PURPOSE: To achieve a physical and clinical comparison between two systems: a screen-film plate and a dual-side computed radiography system (CRM; FUJIFILM FCR 5000 MA). MATERIAL AND METHODS: A unique feature of the FCR 5000 MA system is that it has a clear support medium, allowing light emitted during the scanning process to be detected on the "back" of the storage phosphor plate, considerably improving the system's efficiency. The system's physical performance was tested by means of a quantitative analysis, with calculation of the modulation transfer function, detective quantum efficiency, and contrast-detail analysis; subsequently, the results were compared with those achieved using a screen-film system (SFM; Eastmann Kodak MinR-MinR 2000). A receiver operating characteristic (ROC) analysis was then performed on 120 paired clinical images obtained in a craniocaudal projection with the conventional SFM system under standard exposure conditions and also with the CRM system working with a dose reduced by 35% (average breast thickness: 4.3 cm; mean glandular dose: 1.45 mGy). CRM clinical images were interpreted both in hard copy and in soft copy. RESULTS: The ROC analysis revealed that the performances of the two systems (SFM and CRM with reduced dose) were similar (P>0.05): the diagnostic accuracy of the two systems, when valued in terms of the area underneath the ROC curve, was found to be 0.74 for the SFM, 0.78 for the CRM (hard copy), and 0.79 for the CRM (soft copy). CONCLUSION: The outcome obtained from our experiments shows that the use of the dual-side CRM system is a very good alternative to the screen-film system.

Pattern of developing the performance template.

BACKGROUND: The pattern of energy expenditure during sustained high-intensity exercise is influenced by several variables. Data from athletic populations suggest that a pre-exercise conceptual model, or template, is a central variable relative to controlling energy expenditure. AIMS: The aim of this study was to make systematic observations regarding how the performance template develops in fit individuals who have limited specific experience with sustained high-intensity exercise (eg, time trials). METHODS: The study was conducted in four parts and involved measuring performance (time and power output) during: (A) six 3 km cycle time trials, (B) three 2 km rowing time trials, (C) four 2 km rowing time trials with a training period between trials 2 and 3, and (D) three 10 km cycle time trials. All time trials were self-paced with feedback to the subjects regarding previous performances and momentary pace. RESULTS: In all four series of time trials there was a progressive pattern of improved performance averaging 6% over the first three trials and 10% over six trials. In all studies improvement was associated with increased power output during the early and middle portions of the time trial and a progressively greater terminal rating of perceived exertion. Despite the change in the pattern of energy expenditure, the subjects did not achieve the pattern usually displayed by athletes during comparable events. CONCLUSIONS: This study concludes that the pattern of learning the performance template is primarily related to increased confidence that the trial can be completed without unreasonable levels of exertion or injury, but that the process takes more than six trials to be complete.

Maternal plasma corticotropin-releasing factor (CRF) and CRF-binding protein (CRF-BP) levels in post-term pregnancy: effect of prostaglandin administration.

OBJECTIVE: Placental corticotropin-releasing factor (CRF) affects myometrial contractility and the secretion of several uterotonins such as prostaglandins (PGs); however, the activity of CRF is counteracted by CRF-binding protein (CRF-BP). At term and pre-term labor, CRF levels in maternal plasma are highest whereas those of CRF-BP are falling, and the cause of this fall is unknown. Thus, in this study, we investigated the effect of PG administration for labor induction on maternal plasma CRF and CRF-BP concentrations. DESIGN: Maternal plasma CRF and CRF-BP levels were assayed before and after (2 h later) induction of labor by intracervical administration of prostaglandin E(2) (PGE(2)), and at delivery in a group of healthy post-term pregnancies (n=18). Controls were women at term out of labor (n=22), who subsequently progressed to deliver a healthy singleton baby. METHODS: CRF was measured by two-site immunoradiometric assay, and CRF-BP was assayed by radioimmunoassay. RESULTS: Maternal plasma CRF levels were significantly (P<0.0001) lower and CRF-BP significantly (P<0.0005) higher in post-term than in term pregnancies. With respect to induction of labor, 2 mg PGE(2) were sufficient to increase maternal plasma CRF levels at delivery (P<0.005). While 0.5 mg PGE(2) significantly decreased maternal plasma CRF-BP levels at delivery (P<0.001), 2.0 mg PGE(2) significantly reduced CRF-BP concentrations both after 2 h (P<0.05) and at delivery (P<0.0001). CONCLUSIONS: In the light of the well-known stimulation of prostaglandin release by CRF, these data suggest a positive feedback effect of PGE(2) on maternal CRF release during induced labor.

CHOP-rituximab with pegylated liposomal doxorubicin for the treatment of elderly patients with diffuse large B-cell lymphoma.

Thirty untreated patients, median age 69 years (range 60 - 75 years), with diffuse large B-cell lymphoma (B-DLCL) were treated with a pegylated liposomal doxorubicin (PL-doxorubicin) modified CHOP-rituximab regimen. PL-doxorubicin 30 mg/m2, was given in combination with standard dosage of prednisone, vincristine, cyclophosphamide, rituximab (according to CHOP-R regimen) every 21 days for six courses. Cardiac toxicity was evaluated by mean of echocardiography for left ventricular ejection fraction (LVEF) evaluations and serum troponin-I levels. Overall response and complete response rates were 76% and 59%. Projected two year event free survival and overall survival are 65.5% and 68.5%. No treatment-related mortality was documented. WHO grade III-IV neutropenia and thrombocytopenia were 86% and 3%. Extra-hematological III-IV toxicity was represented, respectively, by a single case of infection, mucositis, and bleeding. LVEF evaluations and the troponin levels did not show significant changes over the course of the treatment. One patient with a previous history of atrial fibrillation experienced a single episode of arrhythmia. None of the patients developed palmar-plantar erythrodysesthesia. This regimen appears an active regimen for the treatment of elderly patients with B-DLCL. The replacement of conventional doxorubicin with PL-doxorubicin seems to be associated with a negligible incidence of extra-hematological toxicity, in particular cardiac and infectious complications.

Physicians' attitudes to the pharmacological treatment of patients with stable angina pectoris.

BACKGROUND: Little is known about how physicians' knowledge of and attitudes to practice guidelines for stable angina may influence their implementation. AIM: To explore the association between physicians' demographics, their knowledge, and opinions about stable angina and their self-reported adherence to guideline recommendations. DESIGN: Questionnaire-based survey. METHODS: We surveyed 1228 Quebec physicians using a questionnaire based on the 'awareness-to-adherence' conceptual framework to measure their adherence with recommendations for the pharmacological treatment of stable angina. Independent predictors of adherence with the targeted recommendations were determined by stepwise linear regression analysis. RESULTS: We received 877 (71.4%) responses from the 1228 eligible physicians. More than 90% of respondents were aware of and agreed with the targeted recommendations. However, the adoption rate varied, even among physicians who generally agreed with the guidelines. Factor analysis indicated that most physicians agreed with recommendations concerning ASA. More negative attitudes were expressed toward beta-blockers and hypolipaemic drugs. Respondents trusted the recommendations of a variety of scientific and professional organizations. Awareness, agreement, and adoption were the strongest predictors of adherence for the three recommendations. Physician demographics and practice characteristics did not predict adherence. DISCUSSION: Physicians were aware of and agreed with the recommendations, so additional large-scale dissemination of the guidelines would be unlikely to improve prescription patterns. However, negative attitudes about beta-blockers and hypolipaemic therapy affected adherence to recommendations for these drugs. Continuing medical education interventions involving local opinion leaders might address some of the obstacles identified.

Drug treatment of stable angina pectoris and mass dissemination of therapeutic guidelines: a randomized controlled trial.

BACKGROUND: Public agencies responsible for implementing health care policies often adapt and disseminate clinical practice guidelines, but the effectiveness of mass dissemination of guidelines is unknown. AIM: To study the effects of guideline dissemination on physicians' prescribing practices for the treatment of stable angina pectoris. DESIGN: Randomized controlled trial. METHODS: A sample of 3293 Quebec physicians were randomly assigned to receive a one-page summary of clinical practice guidelines on the treatment of stable angina (in February 1999), to receive the summary and a reminder (in February and March 1999, respectively), or to receive no intervention (controls). The prescribing profiles of participants, as well as sociodemographic characteristics of the physicians and their patients, were examined for June-December 1999. RESULTS: The intervention had no effect on prescription rates of beta-blockers, antiplatelet agents, or hypolipaemic drugs. Compared to 1997 data for the same physicians, there was an overall 10% increase in appropriate prescription rates, irrespective of the intervention. DISCUSSION: In-house production and dissemination of clinical practice guidelines may not improve physicians' practice patterns if there is pre-existing substantial scientific consensus on the issue.

Update on conservative management of acoustic neuroma.

OBJECTIVE: To update the authors' experience with conservative management of acoustic neuromas. STUDY DESIGN: Retrospective chart review. SETTING: Private practice and tertiary care referral setting. INTERVENTION: Of 600 patients with acoustic neuroma, 102 were treated with the "wait and scan" treatment option. At least two magnetic resonance imaging scans were required of all patients. MAIN OUTCOME MEASURES: Change in tumor size over time was evaluated, as were clinical symptoms: hearing status, tinnitus, balance disturbance, aural fullness, vertigo, headache, and facial pain, numbness, or weakness. RESULTS: Of 102 patients, the average follow-up time interval was 28.5 months. Forty-five (44%) of 102 patients demonstrated a change in tumor size: an average total growth of 2.17 mm per year. In the remaining 54 patients (53%), no growth was demonstrated during a mean follow-up of 28.5 months. Three patients demonstrated actual tumor shrinkage. Of the 102 patients receiving conservative treatment, 85 (84%) reported hearing loss, 67 (66%) tinnitus, 37 (36%) balance disturbance, 29 (28%) aural fullness, 28 (27%) vertigo, 7 (7%) headache, 4 (4%) facial numbness, 2 (2%) facial weakness, and 0 (0%) facial pain. CONCLUSION: Conservative management-"wait and scan"-for selected patients with acoustic neuroma is a reasonable choice of management instead of radiation or microsurgery. In some situations the individual morbidities associated with surgery or radiation make those treatments not in the patient's best interests. A third option is necessary in patients who cannot or do not wish to undergo those other treatments.

Are patients suffering from stable angina receiving optimal medical treatment?

There is good evidence for the use of antiplatelet, beta-blocker and lipid-lowering drugs in the treatment of ischaemic heart disease, but few data on how these medications are used in treating stable angina pectoris. We examined prescription profiles for a sample of patients aged > or =65 years with stable angina, to compare the profiles to local guidelines and to explore the determinants of these profiles, in a cross-sectional study. We identified 11 141 individuals from the Quebec provincial out-patient pharmaceutical database for the period 1 June 1996 to 31 May 1997, and examined the percentage of these patients with and without associated co-morbidities receiving antiplatelet, beta-blocker and lipid-lowering medications. We used hierarchical modelling to examine the role of patient and physician characteristics in explaining the variation in the use of these medications. Calcium-channel blockers were the class of anti-ischaemic drugs most prescribed (63%). Beta-blockers were prescribed in 52.1% of patients. Antiplatelet and lipid-lowering drugs were prescribed to 56.8% and 32.6%, respectively. Increasing age and female gender made patients less likely to be prescribed these treatments. General practitioners were less likely than cardiologists to prescribe beta-blockers and lipid-lowering drugs (OR 0.79, CI 95% 0.68-0.91 and OR 0.77, CI 95% 0.66-0.91, respectively). There is a general under-use of antiplatelet, beta-blocker and lipid-lowering medications in the treatment of stable angina pectoris patients, possibly leading to adverse patient outcomes.

Telehealth: passing fad or lasting benefits?

Advocates of telehealth argue that the delivery of health services by means of communications technologies is both feasible and desirable. Nevertheless, the benefits of telehealth, due to the variety of its applications and their uneven development, are not self-evident. The goal of this paper is to reflect on the processes by which telehealth applications do or do not contribute to the delivery of health services. We propose a framework structuring a preliminary analysis of the match between needs and the possibilities offered by telehealth. Four mechanisms of expected benefits are discussed: 1) decreasing patient transfers; 2) decreasing trips by providers and patients; 3) meeting the needs of underserved populations; and 4) building providers' and patients' knowledge and reducing rural isolation. We conclude by stressing that the participation of providers is crucial, both in the research on telehealth and in the steering of its evolution.

Prevalence and risk factors of Helicobacter pylori-negative peptic ulcer: a multicenter study.

Peptic ulcer disease (PUD) has been described in the absence of Helicobacter pylori (Hp) infection, suggesting that different factors are involved in its etiopathogenesis. We investigated prevalence and characteristics of Hp-negative (Hp-) PUD in an area of Northern Italy and calculated the rate of Hp-positive (Hp+) patients with PUD in whom Hp might be coincidental and not causal. Four hundred nine consecutive patients with endoscopically diagnosed PUD were enrolled in seven hospitals. Hp infection was assessed by rapid urease test and histologic examination. The attributable risk percentages in different age groups were calculated by appropriate formulas. Of 409 patients, 31 (7.6%) were Hp- (gastric, 8.3%; duodenal, 7.6%). Age, nonsteroidal antiinflammatory drug (NSAID) consumption, and complication rates were significantly higher in Hp-than Hp+ patients with duodenal ulcers (DUs). Of the Hp-patients with DU, 58% did not use NSAIDs. In patients with Hp+ DU, the attributable risk percentage for Hp infection in patients aged <40 years, 40-60 years, or >60 years was 98%, 88%, and 66%, respectively. The prevalence of Hp- PUD was about 8%, mainly unrelated to any known etiologic factor. In about one-third of Hp+ patients with PUD aged over 60 years, Hp infection might be coincidental and not causal.

Stereotactic radiosurgery for acoustic neuromas: a survey of the American Neurotology Society.

OBJECTIVE: The purpose of this study was to better understand the complications, outcomes, and surgical difficulties in treating acoustic neuroma patients who have undergone stereotactic radiosurgery (SRS). STUDY DESIGN: A six-page, 28-item questionnaire was mailed to 395 members of the American Neurotology Society. SETTING: The study was conducted through an academic neurotologic practice. Questionnaire respondents were neurotologic physicians in private and academic practice. PATIENTS: A total of 46 patients who had undergone SRS were evaluated. INTERVENTIONS: Twelve (26%) of the 46 patients required microsurgery after SRS. MAIN OUTCOME MEASURES: Posttreatment cranial nerve status and the development of complications such as cerebrospinal fluid leak, meningitis, and cerebrovascular accident were evaluated. RESULTS: In the group of 12 patients who underwent microsurgery after SRS, 11 patients had some form of postoperative facial paralysis. Anacusis was present in all 12 patients. Two of the 12 patients had new-onset trigeminal neuropathy postoperatively. CONCLUSION: Microsurgical resection of acoustic neuroma after SRS is technically difficult. The difficulty exists regardless of the time of microsurgical resection after SRS. Patients who underwent microsurgery after SRS had uniformly poor cranial nerve results.

Evaluation of three intraoperative auditory monitoring techniques in acoustic neuroma surgery.

OBJECTIVE: To assess the efficacy of three intraoperative auditory monitoring techniques: auditory brainstem response (ABR), electrocochleography (ECoG), and direct eight nerve monitoring (DENM). STUDY DESIGN: A retrospective review of the intraoperative recordings of ABR, ECoG, and DENM was performed. SETTING: A private, neurotologic practice. PATIENTS: Sixty-six patients with usable preoperative hearing underwent intraoperative auditory monitoring with ABR, ECoG, or DENM. INTERVENTIONS: Intraoperative auditory monitoring. MAIN OUTCOME MEASURES: Postoperative pure-tone hearing threshold and word recognition scores. RESULTS: Of the 66 patients, 16 (24%) had postoperative serviceable hearing. Five (18%) of the 28 with ABR monitoring, 3 (17%) of the 18 with ECoG monitoring, and 8 (40%) of the 20 with DENM monitoring had serviceable hearing after surgery. CONCLUSIONS: This study suggests that DENM may be more effective than ABR or ECoG, although the differences in hearing preservation rates are not statistically significant.

Randomized trial of fludarabine versus fludarabine and idarubicin as frontline treatment in patients with indolent or mantle-cell lymphoma.

PURPOSE: A first comparative trial of fludarabine (FLU) alone versus FLU plus idarubicin (FLU-ID) for indolent or mantle-cell lymphomas. PATIENTS AND METHODS: From September 1995 to July 1998, 199 patients aged 25 to 65 years (median, 54 years) with newly diagnosed stages II to IV indolent or mantle-cell lymphomas (standard risk according to the International Prognostic Index) were enrolled onto a multicenter, 1:1 randomized study. Of the 199 patients who were able to be assessed, 101 were assigned to the FLU group (six monthly cycles of FLU 25 mg/m(2)/d on days 1 through 5) and 98 to the FLU-ID group (six monthly cycles of FLU 25 mg/m(2)/d on days 1 through 3 and idarubicin 12 mg/m(2) on day 1). RESULTS: In the FLU group, complete response (CR) and partial response rates were 47% and 37%, respectively, whereas in the FLU-ID group, they were 39% and 42%, respectively. In-depth analysis of the CR rate with respect to histologic type showed that FLU seemed to be superior to FLU-ID in treating follicular lymphomas (60% v 40%, respectively), whereas FLU-ID seemed to be more effective than FLU in treating nonfollicular lymphomas (small lymphocytic, 43% v 29%, respectively; immunocytoma, 38% v 23%, respectively; P = not significant), excluding the mantle-cell subset (in which there was no difference between the two groups). No striking differences were observed between the two protocols in terms of overall response or toxicity, which was generally mild. However, with a median follow-up of 19 months, only 29 patients (62%) who received FLU alone have maintained their initial CR, compared with 32 (84%) of those who received FLU-ID therapy (P =.021). CONCLUSION: Although the FLU-ID regimen may not significantly improve the induction of CR in most indolent-lymphoma patients, our preliminary data do suggest that, with respect to FLU alone, it may be capable of conferring a longer-lasting CR and that it might be superior in terms of CR rate in small lymphocytic and immunocytoma subtypes.