Systematic review of the registered clinical trials for oncological hyperthermia treatment.

BACKGROUND: The use of heat to treat various diseases is called hyperthermia treatment (HT). Since the 1970s, the anti-cancer effects of HT have been investigated. Different HT techniques can be categorized as local, regional and whole-body hyperthermia treatment (WBHT). We aim to provide a summary of recent research done on HT to treat cancer. METHODS: In July 2020 ClinicalTrials.gov were systematically searched for all trials including hyperthermia and cancer registered between 2000 and 2020. Studies were excluded when they did not concern hyperthermal treatment, when they were not oncological studies, when they were observational or other non-interventional studies. RESULTS: Of 1654 identified trials, 235 were included. Of these 235 studies, 123 described the use of HIPEC (52.3%), 44 other types of regional HT (18.7%), 45 local HT (19.1%) and 15 WBHT (6.4%). A steady increase (720%) in research to hyperthermic intraperitoneal chemotherapy (HIPEC) can be observed in the last decade. Although HIPEC is the most researched HT modality, an evolution in other HT technologies could be observed during the past decade. CONCLUSIONS: Research to HT to treat cancer has expanded fast. Some techniques, for example HIPEC start to be used outside of research context, but overall, more research is needed to establish a clear effect of these HT techniques.

Tolerability of long-term temperature controlled whole-body thermal treatment in advanced cancer-bearing dogs.

Aim: In oncology, thermal therapy is the application of external heat to fight cancer cells. The goal of whole-body thermal treatment (WBTT) is to raise the patient's core temperature to 39-42 °C, and represents the only thermal treatment modality that can act on both the primary tumor and distant metastases. However, WBTT carries potential risks for toxicity when applied without accurate thermometry and monitoring.Methods: ElmediX has developed a medical device, HyperTherm, to deliver long-term controlled and accurate WBTT (41.5 °C, up to 8 h). The safety of the device and thermal treatment protocol was initially evaluated in minipigs, and we present the confirmation of tolerability of WBTT in dogs with advanced cancer, in combination with a reduced dose of radiotherapy or chemotherapy.Results: Thermometry in liver, rectum, and tumor confirmed a homogeneous heating of these body parts. Monitoring of clinical parameters showed acceptable and reversible changes in liver, cardiac, muscle and coagulation parameters, as was expected. Combination of WBTT with both radiotherapy and chemotherapy only caused some low-grade adverse events.Conclusion: We conclude that our findings support the safe use of HyperTherm-mediated WBTT for canine patients with advanced malignancies. They also tend to support a genuine therapeutic potential for long-term WBTT which needs to be confirmed on a larger dog patient population. Combined with previously reported safety results in minipigs, these contribute to support the ongoing clinical evaluation of WBTT in advanced human cancer patients.

Counting of platelet derived growth factor and transforming growth factor-beta in platelet-rich-plasma used in jaw bone regeneration.

AIM: Growth factors (GFs) as platelet derived growth factor (PDGF) and transforming growth factor (TGF-beta), found in platelet beta-granules also present in platelet-rich-plasma (PRP), accelerate bone revascularization and regeneration and for this reason they have been employed successfully in dental and maxillofacial surgery. Platelet concentrate is commonly used for this purpose as long as platelet release reaction and the consequent GFs loss are avoided. To reduce this phenomenon we set up an easy and fast procedure for preparing a satisfying clotted PRP by adding CaCl2 only (no exogenous thrombin). METHODS: ELISA essay has been used to measure PDGF and TGF-beta in plasma, platelets and serum and platelet GMP-140, with the cytofluorometric technique in order to quantify the degranulation entity. RESULTS: In the 13 examined patients receiving clotted PRP to enhance bone regeneration in post-extractive alveolar sockets, PRP showed no sign of platelet activation (degranulation) and short recalcification times (8-12 min). The autologous clotted PRPs specimen have been evaluated in laboratory in terms of GFs percent: 76% of initial GFs content could be recovered in clotted PRP. This result confirms the absence of platelet degranulation in our procedure. CONCLUSIONS: Significant clinical results in alveolar bone regeneration are reached only with a high percentage of GFs inserted in bone matrix, avoiding early platelet degranulation.

The effects on pupil size and accommodation of sympathetic and parasympatholytic agents.

The time-response effect of two currently used mydriatics, phenylephrine and tropicamide, were evaluated in 524 eyes. Four different types of dilating regimens were used: 2.5% phenylephrine, 10% phenylephrine, 0.5% tropicamide, and the combination of 2.5% phenylephrine and 0.5% tropicamide. The analysis indicated that the recovery from mydriasis occurs between 5.5 and 7.0 hours with 2.5% phenylephrine and at more than 7 hours with 10% phenylephrine. The 0.5% tropicamide induced rapid dilation, whereas the combined treatment, 2.5% phenylephrine plus 0.5% tropicamide, produced the largest maximum pupillary diameter. Tropicamide, alone or in combination, also produced a longer mydriatic effect, lasting more than 7.0 hours. The recovery from the cycloplegic effect of the mydriatics occurred between five and seven hours in the majority of patients, with tropicamide alone or in combination with phenylephrine requiring the most time to revert to normal ranges of accommodation. The findings in this study indicate that, in normal subjects, the recovery from the effect of mydriatic agents is longer than what is generally reported in the literature.

HLA-B35 is associated with accelerated progression to AIDS.

To investigate the influence of HLA specificities on the rate of progression and outcome of human immunodeficiency virus (HIV) infection, we performed (a) a case-control study in 1989-1990 of HIV-seropositive individuals stratified by both risk behavior and ethnic background, (b) a longitudinal cohort study of HIV-infected male homosexuals enrolled in 1981-1982, and (c) an analysis of individuals with a diffuse infiltrative CD8 lymphocytosis syndrome. In the case-control study, there was a significantly higher frequency of HLA-B35 among intravenous drug users, but not homosexuals, who developed illnesses meeting the case definition for AIDS compared with asymptomatic HIV-positive controls, regardless of ethnic status. In the longitudinal study, HLA-B35-positive homosexuals had a significantly increased rate of progression to AIDS and decreased survival over a 7-year period compared with those without this specificity. Finally, there was a significantly decreased frequency of HLA-B35 in individuals with the diffuse infiltrative lymphocytosis syndrome, a clinically and genetically distinctive disorder occurring in HIV infection in which a low rate of progression to opportunistic infections was found. The high rate of salivary and lacrimal gland lymphoma in this group suggests that there is dissociation between the presence of HLA-B35 and the development of particular AIDS-defining conditions. We conclude that HLA-B35 is a risk factor for more rapid progression to AIDS, particularly opportunistic infections and Kaposi's sarcoma, operating in groups with high rates of newly acquired HIV infections such as New York City male homosexuals in 1981-1982, and intravenous drug users in 1989-1990.(ABSTRACT TRUNCATED AT 250 WORDS)

An approach to the human immunodeficiency virus-positive patient with a spondyloarthropathic disease.

One of the unanticipated consequences of infection with the human immunodeficiency virus (HIV) is the appearance of various rheumatic syndromes that traditionally have been thought to result from inappropriate overactivity of the immune system. This distinctive spectrum of rheumatic syndromes has been well described; however, the therapeutics and specific patient management as well as the significance of these disorders for diagnostic classification of the rheumatic disorders have not received a great degree of attention. This article focuses on these areas with emphasis on (1) the nosology of the arthrocutaneous musculoskeletal syndromes with HIV, (2) clinical presentation of the various syndromes, (3) current concepts regarding the etiopathogenesis of the spondyloarthropathic form of arthritis in this setting, and (4) an approach to therapy.

A diffuse infiltrative CD8 lymphocytosis syndrome in human immunodeficiency virus (HIV) infection: a host immune response associated with HLA-DR5.

STUDY OBJECTIVE: To describe the clinical, immunologic, and immunogenetic features of a diffuse infiltrative lymphocytic disorder resembling Sjögren syndrome in persons infected with human immunodeficiency virus (HIV). DESIGN: Clinical case study. SETTING: University-affiliated hospitals and outpatient clinics. PATIENTS: Consecutive sample of 17 patients. MEASUREMENTS AND MAIN RESULTS: All of the 17 patients had bilateral parotid gland enlargement; 14 had xerostomia and 6 had xerophthalmia. Of the 17 patients, 14 had generalized lymphadenopathy, 10 had histologically proved lymphocytic interstitial pneumonitis, 4 had neurologic involvement, and 3 had lymphocytic infiltration of the gastrointestinal tract. Gallium scanning in all of 11 tested patients showed abnormal salivary gland uptake. Minor salivary gland biopsies showed more than 2 lymphocytic foci per 4 mm2 tissue in all of 11 tested patients, the infiltrate consisting predominantly of CD8 cells. Fifteen patients had circulating CD8 lymphocytosis; the principal phenotype of these cells was CD8+ CD29+. Rheumatoid factor and antinuclear antibodies were infrequent, and none of the patients had anti-Ro/SS-A or anti-La/SS-B antibodies. HLA-DR5 was significantly more frequent in the black patients (10 of 12) compared with controls (13 of 45). Only one patient developed an opportunistic infection during 544 patient-months of study, and none has died of AIDS. CONCLUSIONS: A distinct syndrome primarily characterized by parotid gland enlargement, sicca symptoms, and pulmonary involvement occurs in HIV infection. This disorder is associated with CD8 lymphocytosis and the presence of HLA-DR5, and appears to be a genetically determined host immune response to HIV.

A sicca syndrome in HIV infection: association with HLA-DR5 and CD8 lymphocytosis.

A sicca syndrome with parotid enlargement, pulmonary insufficiency, and lymphadenopathy was seen in 12 patients infected with human immunodeficiency virus (HIV), only 1 of whom has had an opportunistic infection during 304 patient months of study. There was a striking increase in numbers of circulating CD8 lymphocytes and the prevalence of HLA-DR5 was greatly increased. In patients with this diffuse infiltrative lymphocytosis syndrome (DILS) the CD8 lymphocytosis, which probably depends on histocompatibility antigen status, may influence disease progression in HIV infection.

Aspects of the spectrum, prevalence and disease susceptibility determinants of Reiter's syndrome and related disorders associated with HIV infection.

Arthrocutaneous disorders including Reiter's syndrome, psoriasiform rashes, and other forms of chronic arthritis and enthesopathy, such as psoriatic arthritis, occur with an increased prevalence in the setting of HIV infection. Herein we describe the spectrum and prevalence of musculoskeletal and allied skin disorders as they occur in the setting of HIV infection. The role of genetic susceptibility in the development of these disorders is addressed. Based on the frequency of infectious agents capable of triggering reactive arthritis and the presence of HLA-B27 in 71% of these individuals, it is suggested that the disorder strongly resembles Reiter's syndrome as it occurs in the not HIV-infected group. Preliminary evidence indicates an enhanced penetrance for susceptibility among HLA-B27 individuals. In contrast, among HIV-infected patients with psoriasiform lesions there was no statistically significant association (P less than 0.05) between the presence of psoriasiform rash and the HLA alleles Cw6, B7, B17, Bw16, or Bw57 when compared with HIV-infected controls. These findings suggest that among HIV-infected individuals the development of Reiter's syndrome involves an immune recognition event primarily dependent upon HLA-B27 molecules in which an unknown antigen in the context of HLA-B27 is presented to CD8 lineage suppressor/cytotoxic cells. In contrast, the pathogenesis of psoriasiform lesions in HIV patients, despite their similarity to certain lesions in Reiter's syndrome, proceeds by distinct pathways that do not involve events influenced by specific polymorphic class I molecules.

Implications from the occurrence of Reiter's syndrome and related disorders in association with advanced HIV infection.

Information bearing on the prevalence and character of Reiter's syndrome and allied disorders as they occur in a setting of HIV infection was reviewed. Based on the frequency of infections by organisms capable of inducing reactive arthritis and the presence of HLA-B27 in 71% of the individuals, it was concluded that the disorder strongly resembled Reiter's syndrome occurring in the non-HIV infected group. Preliminary evidence suggested an enhanced penetrance of susceptibility among HLA-B27 individuals. In view of the preservation of CD8 lineage T cells and functional loss of CD4 lineage T cells in HIV-infected patients, it was suggested that a specific immune recognition event is at the center of the pathogenesis of this syndrome which involves preservation of an unknown antigen in the context of HLA-B27 to CD8 lineage suppressor/cytotoxic T cells.

[Chlorhydropeptic inhibition with atropine during stimulation with pentagastrin. A possibility of selective evaluation of gastric secretive function]. / L'inhibizione cloridropeptica da atropina in corso di stimolazione con pentagastrina. Una possibilità di valutazione selettiva della funzione secretiva gastrica.

Basal secretion and the acidity peak have been evaluated in ulcerous patients during pentagastrinic stimulation and during atropinic inhibition, on the basis of the observations of Schofield et al. and in relation to the need to achieve correct identification and quantification of hydrochloric acid gastric secretive function. The results obtained with this technique suggest the possibility of a selective evaluation of the secretive function of oxyntic cells. This is extremely interesting because it opens the way to the most suitable surgical techniques for the treatment of ulcers.

[Calcitonin inhibition of insulin-stimulated gastric secretion. A possibility of selective evaluation of gastric secretory function]. / Sull'inibizione calcitoninica della secrezione gastrica da stimolazione insulinica. Una possibilità di valutazione selettiva della funzione secretiva gastrica.

There is both clinical and experimental evidence for the antigastric effect of calcitonin. A study was therefore made of gastric secretion after maximum insulin stimulation, and during its inhibition by calcitonin. Evaluation of basal acid flow and the maximum acidity peak in these two tests showed that the difference between the two peaks was related to the increase in gastrin. This was not the case during inhibition. The results show that selective evaluation of gastric secretion enables selective surgical techniques to be employed in the treatment of duodenal ulcer.