Hand grip support for rehabilitation and assistance: from patent to TRL5.

In the last decades, the continuous increase in the number of the vast cohort of chronic patients that constantly need medical assistance and supervision, and the widespread lack of therapist has brought to an increased interest in the role of medical technologies in rehabilitative programs and assistive scenarios. Current clinical evidence in rehabilitation demonstrates that there is an important and increasing demand for innovative therapeutic solutions to recover the hand functions to prevent patients to need assistance in performing daily life activities. This works describes the pathway from patent to TRL5 of a device to support hand grip actions and interaction with daily life objects. E-KIRO is based on the use of electromagnets, which are able to attach/detach interactive objects equipped with a ferromagnetic plate. Five end-users used the device and scored it with excellent usability based on the System Usability Scale.

Carboplatin, doxorubicin, and cyclophosphamide versus cisplatin, doxorubicin, and cyclophosphamide: a randomized trial in stage III-IV epithelial ovarian carcinoma.

One hundred sixty-four patients with stage III-IV epithelial ovarian carcinoma were randomized to receive cisplatin (CDDP) 50 mg/mq, doxorubicin 45 mg/mq, and cyclophosphamide 600 mg/mq (PAC) or carboplatin 200 mg/mq, doxorubicin 45 mg/m2, and cyclophosphamide 600 mg/mq (CAC). To administer equitoxic doses at each cycle, the drug dosages were adjusted according to the hematologic toxicities experienced after the previous course; 44.7% of CAC and 21.1% of PAC patients required a dosage reduction at the second course (P = .002). Neither CAC nor PAC caused any clinically relevant neuro-nephrotoxicity; however, CDDP was administered with hydration and forced diuresis, while carboplatin was administered by rapid intravenous (IV) infusion. After six cycles, response rates were superimposable: 62.5% and 66.6% for CAC and PAC, respectively; pathologic complete responses (pCRs) were 16.7% for CAC and 23.2% for PAC; among patients with more than 2 cm residual disease, PAC induced more pCRs than CAC (eight of 52 or 15.4% v one of 42 or 2.4%, P = .07). Median survivals and progression-free survivals (PFSs) were 22.6 and 13.2 months for PAC, and 23.1 and 15.5 months for CAC, respectively; these differences are not significant. In conclusion, this trial demonstrates that equitoxic doses of PAC or CAC result in a similar response rate, PFS, and survival.

High-dose versus low-dose cisplatin in combination with cyclophosphamide and epidoxorubicin in suboptimal ovarian cancer: a randomized study of the Gruppo Oncologico Nord-Ovest.

PURPOSE: The aim of the study was to compare high-versus low-dose cisplatin in combination with cyclophosphamide and epidoxorubicin as primary chemotherapy for suboptimal stage III and IV ovarian cancer. PATIENTS AND METHODS: One hundred forty-five patients were randomized to receive six courses of cisplatin 50 or 100 mg/m2 plus epidoxorubicin 60 mg/m2 and cyclophosphamide 600 mg/m2. The two treatment arms were well balanced; all patients had greater than 2 cm and 37.2% had greater than 5 cm of residual disease; 29.6% had stage IV disease. RESULTS: Patients in the high-dose arm received a double dose-intensity and double total dose of cisplatin. The high-dose regimen induced significantly more episodes of leukopenia (47.8% v 32.8%, P = .05), thrombocytopenia (21.7% v 3.2%, P = .003), anemia (37.6% v 12.5%, P = .002), nephrotoxicity (six v one patient), and neurotoxicity (30.4% v 6.3%, P = .002). There were no significant differences in efficacy in terms of clinical response rate (high-dose 57.5% v low-dose 61.1%), pathologic complete response (CR) (9.6% v 18.1%), median survival times (29 v 24 months), and median progression-free survival (18 v 13 months). CONCLUSION: This study shows that doubling the dose-intensity and total dose of cisplatin in combination with epidoxorubicin and cyclophosphamide has significant toxic effects and does not improve clinical outcome in patients with suboptimal ovarian cancer.

Increased cyclin D1 expression is associated with features of malignancy and disease recurrence in ovarian tumors.

Alterations in the expression of cyclin D1 have been reported frequently in several human cancers, but their significance in the multistep model of carcinogenesis has been scantly described. To define the pattern of cyclin D1 expression in the development of ovarian cancer and clinical outcome, 55 cases of benign ovarian tumors, 12 borderline cases, and 37 ovarian carcinomas (32 primary and 5 recurrent carcinomas) were studied. Analyses were carried out on fresh tumor specimens by Western blotting and reverse transcription-PCR and provided significant superimposable results (P = 0.00001). Cyclin D1 abundance was classed according to the densitometric values as undetectable, detectable, well detectable, and highly detectable. A significant increase (P < 0.000001) in median cyclin D1 values was observed from benign (0.038; range, 0.001-0.705) to borderline (0.226; range, 0.001-0.623) to malignant (0.347; range, 0.027-2.330) to recurrent (0.887; range, 0.309-2.2260) tumors. In addition, higher median cyclin D1 values were reported in serous carcinomas (P = 0.058) and advanced-stage diseases (P = 0.003). Survival analyses carried out in the 32 primary carcinomas showed no significant difference in overall survival between detectable versus well/highly detectable cyclin D1 neoplasms. Conversely, a significant relationship between cyclin D1 expression and progression-free survival was found (P = 0.031). These results may elucidate the function of altered cyclin D1 expression in ovarian tumorigenesis and provide a basis for additional studies on its prognostic role.

Adjuvant cisplatin-based chemotherapy for stage I and II ovarian cancer: a 7-year experience.

87 patients with high risk of recurrence FIGO stage I and II ovarian carcinoma were treated with adjuvant chemotherapy consisting of cisplatin 50 mg/m2 plus cyclophosphamide 600 mg/m2 on day 1 every 28 days for 6 courses. Toxicity and efficacy of the regimen was evaluated after a median follow-up of 45 months. Treatment-related toxicity was mild and reversible, consisting chiefly of acute WHO grade 2 myelosuppression (10% of patients) and controllable grade 3 emesis (55%). No late toxicity was observed. Actuarial 7-year survival and relapse-free survival (RFS) were 76% and 61%, respectively; a statistically significant difference in outcome was observed for undifferentiated grade tumour (G1 vs. G2 vs. G3: P less than 0.01) but not for FIGO stage disease (stage I vs. stage II). In our opinion, short-term chemotherapy including the most active single agent, i.e. cisplatin, appears a tolerable and effective treatment which deserves further evaluation in large randomised trials.

Prospective multicenter study on urologic complications after radical surgery with or without radiotherapy in the treatment of stage IB-IIA cervical cancer.

A national collaborative group has conducted a multicenter prospective study on the use of a specific glossary for the complications associated with the treatment of cervical cancer, which were analytically described in 1989. This report analyzes the urologic complications with particular reference to radical surgery in stage IB-IIA cancer cases. In the prospective multicenter clinical study 2024 patients with frankly invasive cervical cancer were enrolled (IB = 1041; IIA = 308; IIB = 384; IIIA-B = 237; IV = 54). This report considers 1349 patients with stage IB-IIA disease. Treatment modalities in this group of patients were: type III radical surgery in 21.9%; type III radical surgery followed by radiotherapy in 20.8%; type III radical surgery preceded by radiotherapy in 7.3%; type II radical surgery in 3.1%; type II radical surgery followed by radiotherapy in 8.4%; type II radical surgery preceded by radiotherapy in 18.8%; surgery plus chemotherapy plus radiotherapy in 3.5%; radiotherapy alone in 16%. In this case series 873 complications were registered, and among these 341 (39.1%) were described in the urinary tract. Among 277 bladder complications 47.3% were grade 1; 47.3% grade 2, and 5.4% grade 3. Among 64 ureter complications 59.4% were grade 1; 17.2% grade 2, and 23.4% grade 3. Distribution of severe urinary complications was different according to site (bladder or ureter) and treatment modalities (radical surgery alone: bladder 1.3%, ureter 1.3%; radical surgery followed by radiotherapy: 1.4% bladder, 2.8% ureter; radical surgery preceded by radiotherapy: 3% bladder, 0% ureter). Different distributions of severe urinary complication were also observed in respect to stage (IB vs IIA); treatment: elective vs nonelective. In 673 patients treated with radical surgery plus or minus radiotherapy 123 relapses were registered (18.2%). Incidence of relapse was not different in patients suffering from mild/severe complications vs patients without complications. Disease-free survival, death from tumor, and death from other causes were not different in the group with complications in comparison to the group without complications.

Randomized study comparing chemotherapy plus radiotherapy versus radiotherapy alone in FIGO stage IIB-III cervical carcinoma. GONO (North-West Oncologic Cooperative Group).

Between January 1989 and December 1991, 64 patients with advanced cervical carcinoma FIGO stage IIb-III were randomized to receive radiotherapy (RT) alone or the sequential combination of chemotherapy (CT) and RT. RT consisted of external RT (40 Gy fractionated over 4 weeks)+brachy-therapy (40 Gy to point A)+an additional boost to the parameters (15-20 Gy) in arm RT; CT consisted of cisplatin 60 mg/m2 i.v. day 1 q 15 days administered for 2 cycles before the start of RT and for 4 cycles after the end of radiation treatment in CT+RT arm. Among the 58 evaluable patients objective response rate was as follows: in RT arm, CR in 40.7% of patients, PR in 40.7%, and SD in 18.6%; in CT+RT arm, CR in 42% of patients, PR in 35.5%, and SD in 22.5%. The median duration of response was 12 months (range: 3-38 + months). At a median follow-up of 36 months survival (S) and progression-free survival (PFS) were 83% and 72.4% in RT arm, 72% and 59.3% in CT+RT arm, respectively. No significant difference was observed between the 2 treatment arms, neither in terms of objective response nor in terms of S and PFS. Both treatments were generally well tolerated. In our experience the addition of chemotherapy to standard radiotherapy does not enhance morbidity and does not interfere with the correct delivery of the planned treatment. However, results of this combined modality regimen remain unsatisfactory, since no improvement in pelvic control and survival of patients with advanced cervical carcinoma was observed.

Cisplatin and 5-fluorouracil in advanced and recurrent cervical cancer.

Nineteen consecutive patients with advanced or recurrent cervical cancer were treated with cisplatin 20 mg/m2 plus 5-fluorouracil 200 mg/m2 on days 1-5 every 3 weeks. Toxicity was acceptable and manageable, with most patients treated on an outpatient basis. The most important side effect was dose-cumulative neurotoxicity. In 18 evaluable patients a 61% objective response rate (1 complete and 10 partial) was achieved. In recurrent disease the regimen was effective both in irradiated lesions and in non-irradiated ones. Two out of five patients not previously treated with radiotherapy and/or chemotherapy responded to the treatment but tumor regression was insufficient for the disease to be controlled radically by subsequent surgery or radiotherapy. The median duration of response was 11 months (3-23) and the actuarial survival rate after 36 months follow-up was 43.3%.

Histochemical study of mucinous ovarian cystomas of intestinal and mixed types: O-acetylated sialomucin content in relation to biologic behavior.

The subgroup of mucinous ovarian cystomas of intestinal type containing site 8 O-acetylated sialomucins and its relation to malignant behavior were studied. Of 75 mucinous cystomas of the ovary from the files of the Institute of Pathological Anatomy and Histology (University of Genoa), 54 were endocervical, 19 were mixed, and 2 were intestinal. As regards their histologic pattern, the 54 mucinous endocervical cystomas were benign, whereas the 19 mixed type group included 8 benign, 5 borderline and 6 malignant; the 2 intestinal type tumors were borderline. According to histochemical investigations, the frequency of tumors with goblet cells containing site 8 O-acetylated sialomucins (positive to PB/KOH/PAS) was 47% in the mixed type cystomas and 100% in the intestinal type cystomas. Twenty-five percent of benign mixed cystomas, 60% of borderline mixed cystomas, and 67% of mixed cystadenocarcinomas were positive to PB/KOH/PAS. One hundred percent of the borderline cystomas of intestinal type were positive. Our results confirm that among mucinous ovarian cystomas, those containing intestinal type epithelium are the most likely to fall within the borderline or malignant categories. Moreover, of all ovarian cystomas of intestinal type, those characterized by site 8 O-acetylated sialomucins seem to be more aggressive and, in general, to have a more malignant behavior than the mucinous cystic tumors of müllerian or endocervical type.

Carboplatin (JM 8), adriamycin and cyclophosphamide (JAC) in advanced ovarian carcinoma: a pilot study.

Eleven untreated patients with advanced ovarian cancer were studied for tolerance and response to combination treatment with fixed doses of adriamycin (45 mg/m2) and cyclophosphamide (600 mg/m2) + escalating doses of carboplatin. At the first dose level of carboplatin (200 mg/m2), toxicity was acceptable. With carboplatin at 300 mg/m2, severe hematologic toxicity was observed. The dose-limiting toxicity was leukopenia. Although carboplatin was administered without any hydration, no patient experienced renal toxicity. Eight objective responses were observed in 9 clinically evaluable patients. At second look surgery, 3 complete responses and 4 partial responses were documented. Polychemotherapy with JAC (carboplatin, 200 mg/m2, adriamycin, 45 mg/m2, and cyclophosphamide, 600 mg/m2) is administrable with acceptable toxicity.

Treatment of FIGO stage Ib cervical carcinoma with nodal involvement.

One hundred and eighty one patients with stage Ib cervical cancer underwent hysterectomy with pelvic lymphadenectomy. The overall incidence of lymph node metastases was 20%. Twenty seven (71%) patients with nodal involvement were treated by external radiotherapy (TCT) and 11 (29%) by both chemotherapy and radiotherapy (Lin. Acc.). The overall survival at 5 years was 80%; it was 43% for patients with positive nodes and 89% for patients without metastatic nodal disease. The 3 year survival of patients with positive nodes who underwent radiation therapy by TCT was 58%, while it was 72% for those treated by chemotherapy plus radiotherapy. We observed a recurrence in 23% of the cases, 52% in patients with positive nodes and 15% in those with negative nodes. The association chemo-radiotherapy in patients with metastatic lymph nodes seems to improve the survival and reduce the recurrence rate.

Cisplatin-based combination chemotherapy with or without doxorubicin in advanced epithelial ovarian cancer: 8-year update of a randomized multicentric clinical trial. The Gruppo Oncologico Nord Ovest (GONO).

One hundred and twenty-five patients with advanced epithelial ovarian cancer (EOC) were postsurgically included in a multicentric clinical trial comparing the association of cisplatin (CDDP) (50 mg/m2 iv day1) + cyclophosphamide (CTX) (600 mg/m2 iv day 1) (PC regimen) versus the combination of PC + doxorubicin (ADM) (45 mg/m2 iv day 1) (PAC regimen), repeated every four weeks. After the sixth course of chemotherapy, patients without clinical evidence of disease or with surgically resectable residual disease (RD) underwent second-look laparotomy. Afterwards patients in surgical complete response (sCR) stopped chemotherapy, while partial responders or patients with stable disease received six more courses of the same regimen used as first-line treatment. Among the 67 patients with measurable RD, PAC regimen achieved a better clinical complete response (40.6% vs 20.0%); the difference approached statistical significance. In the 75 patients who underwent second-look laparotomy, PAC regimen induced a significantly higher sCR rate (62.2% vs 39.5%, p less than 0.05). The median survival (S) and progression free survival (PFS) were better in PAC arm, even if the differences were not statistically significant. Eight-year S and 8-year PFS were 32.7% and 24.7% respectively, for PAC arm, and 23.9% and 14.1%, respectively, for PC arm. These data seem to confirm the clinical advantage provided by the addition of ADM to PC regimen in the treatment of advanced EOC.

[Preoperative autologous blood donation and transfusion in gynecology]. / Predeposito e trasfusione di sangue autologo in ginecologia.

BACKGROUND: Autologous transfusions reduce the risk of alloimmune and infectious complications of allogenic blood transfusions. We have evaluated preoperative autologous blood donation practice in relation to patients characteristics and surgical technique. METHODS: In the Obstetrics and Gynecology Department of Genoa University, we enrolled 462 patients in an autologous transfusion program during 1997. We did not analyze 105 patients who underwent minor surgery. Patients with hemoglobin lower than 11 g/dl or with other risks related to autotransfusion have been excluded; 284 (79.5%) patients have been able to make preoperative autologous blood donations. Patients who did not undergo predeposit have utilised type screen or cross reaction for a possible who did eterologous transfusion. We have analysed the two groups of patients for kind of pathology, for number of heterologous blood units used, for number of transfused patients and we have considered the mean of the units received by each of them. RESULTS: 44 of the 284 predeposited blood units were reinfused while 10 patients, who did not undergo predeposit, were transfused. Heterologous transfusion was done in 1.06% of the cases that underwent predeposit. Oncologic patients underwent predeposit in 83% of the cases. CONCLUSIONS: We have concluded that autologous blood donation reduces the risk of allogenic blood transfusion especially in oncologic surgery.

Utilizing an epidemiological profile for HIV prevention community planning in West Virginia.

An epidemiologic profile revealed that approximately 1,000-1,600 persons in West Virginia are living with HIV, and that it is the 5th leading cause of death among persons ages 25-44. HIV is also the leading cause of death in black males ages 25-44 in WV, and blacks are disproportionately affected by HIV/AIDS (composing about 3.1% of the general population and 17% of the AIDS population). This is most marked in Kanawha, Raleigh, and McDowell counties. The predominant mode of exposure reported from 1984-1993, and more recently from 1991-1993, has been men having sex with men (MSM), accounting for 57% of all AIDS cases. A substantial proportion of all cases (13%) were attributed to injecting drug use (IDU), especially in Public Health District 1 where 63% of women infected with HIV reported IDU as a risk behavior. It is difficult to draw conclusions about populations at risk in WV because of the large proportion of HIV cases reported without risk behaviors (26.5%). However, among men, most cases initially reported without risk are eventually reclassified to the MSM and IDU categories. Among women, most cases first reported without risk are eventually changed to the IDU and heterosexual contact categories. Map analyses by Public Health District and county suggest some clustering of cases in the southern region of the state which may be secondary to racial/ethnic and sociodemographic factors.

How to separate ionic liquids: use of hydrophilic interaction liquid chromatography and mixed mode phases.

This chromatographic study deals with the development of a convenient and versatile method to separate Room Temperature Ionic Liquids. Different modes of chromatography were studied. The study attempts to answer the following question: "what were the most important interactions for the separation of ionic liquids?". The results show that the essential interactions to assure a good retention of RTILs are the ionic ones and that hydrophobic interactions play a role in the selectivity of the separation. The separation of five imidazolium salt with a traditional diol columns in Hydrophilic Interaction Chromatography (HILIC) was demonstrated. It shows that neutral diol grafted column allows an important retention that we assume is due to the capability of diol to develop a thick layer of water. Furthermore, stationary phase based on mixed interaction associating ion exchange and hydrophobic properties were studied. Firstly, it will be argued that it is possible to separate RTILs with a convenient retention and resolution according to a reverse phase elution with the Primesep columns made of a brush type long alkyl chain with an embedded negatively charged functional group. Secondly, a sucessful separation of RTILs in HILIC mode with a mixed phase column containing a cationic exchanger and a hydrophobic octyl chain length will be demonstrated.