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PubMed2026

Multimodal Therapy With Metformin, Inositol and Dietary Restriction Improves Insulin Resistance and Endocrine Outcomes in Women With Polyendocrine Metabolic Ovarian Syndrome: A Randomized Controlled Trial.

INTRODUCTION: Polyendocrine metabolic ovarian syndrome (PMOS), formerly known as polycystic ovary syndrome (PCOS), is a common endocrine-metabolic disorder characterized by insulin resistance, hyperandrogenism and ovulatory dysfunction. Metformin, inositol supplementation and lifestyle modification are widely used treatments, but direct comparative evidence remains limited. Multimodal therapy combining metformin, inositol and dietary restriction produces greater metabolic and reproductive improvement than single-modality interventions. METHODS: We conducted a 12-week randomized controlled trial in 192 women aged 18-35 years diagnosed with PMOS according to Rotterdam criteria. Participants were allocated to metformin (1500-2000 mg/day), inositol (myo-inositol 2 g plus d-chiro-inositol 50 mg twice daily), calorie-restricted diet (1200-1500 kcal/day), or combination therapy. Primary outcomes included changes in body mass index (BMI) and insulin resistance assessed by HOMA-IR. Secondary outcomes included testosterone, LH/FSH ratio and menstrual regularity. Analysis was performed using analysis of covariance (ANCOVA), with post-intervention values as dependent variables and corresponding baseline values as covariates. Categorical outcomes were compared using the Chi-square test. RESULTS: All interventions improved metabolic and endocrine parameters. Combination therapy resulted in the greatest reduction in HOMA-IR (- 2.64, 95% CI - 2.82 to -2.46, p < 0.001) and BMI (- 2.8 kg/m2, 95% CI - 3.05 to -2.55, p < 0.001). Menstrual cyclicity improved across all groups, with the highest proportion of participants reporting cycle regularisation in the combination therapy group (85.4%), compared with dietary restriction (72.9%), inositol (64.6%), and metformin (39.6%) (p < 0.001). Given the short follow-up duration, these findings reflect early improvements rather than sustained normalisation. CONCLUSION: Multimodal therapy was associated with superior metabolic and reproductive outcomes compared with single-modality interventions in women with PMOS. CLINICAL TRIAL REGISTRATION: ClinicalTrials. gov (NCT07380841).

Humans↗

PubMed1978

L2C guinea pig leukemia. A potential model for structuring multimodality therapy.

L2C guinea pig leukemia is a lymphoblastic neoplasm that arose spontaneously in a nonirradiated female strain 2 guinea pig over 20 years ago. Mutation of the original tumor probably accounts for the discordant results which have been reported. The LE-L2C subline was used to develop a multimodality therapy model of acute leukemia. Syngeneic strain 2 animals challenged with 3 x 10(5) LE-L2C cells developed overt leukemia in 14 +/- 3 (SD) days. When treated with cytoreductive chemotherapy, they relapsed with either systemic or central nervous system (CNS) disease. However, CNS relapse was prevented by craniospinal irradiation, yielding a uniform pattern of relapse. Preliminary studies suggest that active immunotherapy with nonspecific agents, such as BCG, or immunoreconstitution with thymosin may prolong the duration of remission and increase the percentage of long-term survivors. L2C leukemia may represent a useful animal model for structuring the principles that govern the interrelationship between chemotherapy and immunomudulation.

Animals↗

PubMed1979

Metabolic response to surgery in the cancer patient: consequences of aggressive multimodality therapy.

The metabolic response to uncomplicated surgery in the patient undergoing primary therapy for malignancy is no different than the response to surgery of similar magnitude for benign disease. Hemodynamic, nutritional-endocrine, and convalescent changes are similar. However, with current aggressive approaches to the management of cancer, the patient often comes to surgery with evidence of major debilitating side effects from his progressive malignancy or from aggressive multimodality therapy. The surgeon must be aware of the consequences of the use of combination therapies on the expected metabolic response to surgery. Awareness of such problems such as the nutritional deficit will allow preventive methods to supercede metabolic salvage procedures.

Animals↗

PubMed1977

Acute myelogenous leukemia as a late complication of the multimodality therapy for Hodgkin's disease.

Progressive thrombocytopenia developed in a patient following the completion of total lymphoid irradiation and combination chemotherapy for Hodgkin's disease. Thorough evaluation eventually yielded a diagnosis of acute myelogenous leukemia (AML). Previous workers have suggested that the development of thrombocytopenia with a hypoplastic marrow following total lymphoid irradiation indicated recurrent Hodgkin's disease. When the combination cytopenias and hypoplastic marrow is recognized these workers have recommended early combination chemotherapy. Recent data suggest a 1300-fold increase in the risk of AML following multimodality therapy for Hodgkin's disease. We feel that a careful search for AML should be conducted in patients with deteriorating hematologic parameters following therapy for Hodgkin's disease and that this search should include sampling bone marrow outside irradiated areas.

Adult↗

PubMed1979

A follow-up of alcoholics treated by multimodal therapy.

A general hospital sponsored for the psychotherapeutic treatment of alcoholism is described. In this context a multimodal approach, emphasizing methods derived from principles of learning, is applied to training the individual in new life-style skills for the management of alcoholism. Demographic characteristics of the population served by the program are of a predominantly blue collar clientele, mostly employed (72%), married (61%), and from urban centers (95%). Attrition as a major problem in evaluating results at the follow-up stage is identified and a method of reporting follow-up results taking this factor into account is presented. This method showed that under the most stringent conditions for reporting results, 36.64% of a sample of 131 alcoholics were showing improvement at 12 months, while under the least stringent condition 84% were showing some improvement over the same period.

Adult↗

PubMed1977

Preliminary results of aggressive multimodality therapy for metastatic osteosarcoma.

Ten patients with metastatic osteosarcoma were treated at the Joint Center for Radiation Therapy, the Sidney Farber Cancer Institute, and the Children's Hospital Medical Center from 1973 to 1976. Patients were treated with an aggressive multimodality approach with included surgery, chemotherapy, and radiation therapy. Three of 10 patients are alive with no evidence of disease, five are alive, with disease, and two are dead of disease. The median survival is 12+ months. Local control data for radiation combined with high dose methotrexate in metastatic osteosarcoma is shown.

Adolescent↗

PubMed1975

The success and failure of multimodal therapy for cancer in children.

Achievements, as well as limitation, in combination treatment of childhood malignancies are discussed. Tumor types are grouped according to response (definite, probable, unknown) to combined treatment. Improvements in survival rates have occurred following the addition of chemotherapy to surgery and radiation therapy in children with Wilmes' tumor, and Ewing's and soft tissue sarcoma, probably by suppression of microscopic metastases. So far, advances are not yet apparent following multimodal treatment of neuroblastoma, hepatoma, and ovarian tumors.

Adolescent↗

PubMed1977

Blindness during remission in two patients with acute lymphoblastic leukemia: a possible complication of multimodality therapy.

Two patients with acute lymphoblastic leukemia treated on the same protocol became blind during complete remission. Therapy consisted of systemic combination chemotherapy, prophylactic central nervous system irradiation and monthly intrathecal cytosine arabinoside. Eight months after CNS irradiation visual acuity in both patients began to decrease. Meningeal leukemia in the area of the chiasm was suspected but despite additional radiotherapy, steroids and continued intrathecal therapy, both patients were blind within 6 months. Numerous lumbar punctures were negative for leukemic cells. Extensive investigation, including craniotomy in one case, failed to reveal the cause of blindness. Biopsy of the optic nerve in one case was compatible with radiation toxicity. We postulate that potentiation of radiation toxicity to the optic nerves and chiasm by systemic chemotherapy, intrathecal chemotherapy, or both, may have led to blindness. The patients continue in complete hemotologic and CNS remission 12 and 29 months after becoming blind.

Acute Disease↗

PubMed1977

Acute and late effects of multimodal therapy on normal tissues.

The increasing use of combined radiation, chemotherapy, and surgery had led to an increased incidence of acute and late complications. The complications are, in general, similar to those seen with each modality alone, but occur with increased incidence. Enhanced effects of combined radiation and surgery are modest in number and consist primarily of problems with wound healing and fibrosis, as well as late gastrointestinal damage. Combinations of radiotherapy and chemotherapy have shown a greater degree of enhanced acute and late reactions. Drugs, such as actinomycin-D and Adriamycin, are particularly dangerous if the marked enhancement of radiation effects caused by the drugs in almost all organs is not appreciated and the radiation dose not adjusted accordingly. Proper selection of drugs can lead to enhanced local control by radiotherapy and/or surgery, as well as eradication of microscopic distant metastases, without increased normal tissue injury. Late induction of malignancy can occur with either radiation or chemotherapy alone and, in some cases, this appears to be enhanced when they are combined.

Antineoplastic Agents↗

PubMed1979