Immunotherapeutic and immunoregulatory drugs in haematologic malignancies

A better understanding of the biology and pathogenesis of hematological malignancies has led to the development of immunotherapeutic and immunoregulatory drugs. Many of these agents have revolutionized the current treatment modalities, while others are under investigation. Rituximab (anti-CD20 antibody) has been established as the gold standard of treatment for aggressive B-cell lymphomas in combination with CHOP and has shown significant activity as monotherapy in the treatment of indolent B-cell lymphomas. In follicular lymphomas the combination of Rituximab with chemotherapy improves the outcome compared to chemotherapy alone. CD 20-based radioimmunotherapy, with the advantage of the bystander effect, represents an additional therapeutic alternative in B-cell lymphomas and may produce tumor regression in Rituximab resistant patients. The anti-CD52 monoclonal antibody, alemtuzumab, further expands the armamentarium against lymphoid malignancies producing high response rates in these entities. Antibody-targeted chemotherapy such as gemtuzumab ozogamicin, consisting of an anti-CD33 antibody combined to calicheamicin, has shown efficacy in the treatment of refractory acute myeloid leukemia; exact indications, timing and dosing schedule for optimized efficacy remain to be determined. Interferons have proven significant activity in cutaneous lymphomas, hairy cell leukemia and chronic myelogenous leukemia by mechanisms that are not fully elucidated. Thalidomide, by acting as an immunomodulatory and antiangiogenic agent can modulate neoplastic cells microenvironment and lead to disease control in multiple myeloma as well as in numerous other hematological malignancies. Bortezomib, a proteasome inhibitor, displays significant anti-tumor activity, especially in multiple myeloma and lymphoproliferative disorders. The addition of these agents in therapeutic regimens has improved considerably the treatment of hematological malignancies.     

Effect of 2% chlorhexidine gel mixed with calcium hydroxide as an intracanal medication on sealing ability of permanent root canal filling: a 6-month follow-up

The present study was conducted to determine the influence of 2 intracanal medicaments (calcium hydroxide, chlorhexidine gel 2%) when used either alone or combined on the short- and long-term sealing ability of permanent root canal fillings. Ninety human upper central incisors were divided into 4 experimental groups (n=20). All root canals were instrumented in a step-back motion and then treated as follows: group I, root canal dressing with calcium hydroxide for 2 weeks and then obturation with laterally compacted gutta-percha and AH26 sealer; group II, chlorhexidine gel 2% for 2 weeks and obturation as in group I; group III, dressing with a new paste made by mixing calcium hydroxide plus chlorhexidine gel 2% for 2 weeks and obturation as described previously; group IV, immediately obturated with laterally compacted gutta-percha and AH26 sealer. Leakage along root canal fillings was measured using the transport fluid model. Short term measurements were carried out for 3 hours after 24 hours equilibrium establishment. Leakage was measured again at 6 months after the initial measurement. At 3 hours, no significant differences were found among the 4 experimental groups. Long-term measurements showed that also at 6 months no significant differences were observed between the group IV and the other 3 experimental groups. Under the conditions of the present study, it could be supported that none of the medications used seemed to affect negatively neither the short- nor the long-term sealing ability of the tested obturation technique. On the basis of these results and because of its increased antimicrobial action as it is supported in the literature, the new paste made of calcium hydroxide plus chlorhexidine gel 2% can be proposed for use in clinical practice without affecting the sealing ability of root canal obturation.     

Fungal endophthalmitis caused by Paecilomyces variotii following cataract surgery: a presumed operating room air-conditioning system contamination

PURPOSE: To report a case of delayed fungal endophthalmitis by Paecilomyces variotii following uncomplicated cataract surgery. To our knowledge this is the first reported case of postoperative endophthalmitis by this species. METHODS: We report the longterm clinical follow-up of an 83-year-old female who underwent uncomplicated sutureless, small-incision cataract surgery. She developed recurring uveitis 4 months after surgery. Vitreous tap and finally complete vitrectomy with removal of the capsular bag including the intraocular lens were performed. Fungi were studied by histopathology and culture. RESULTS: At histopathological examination, the fungi were found to be closely related with the capsular bag. A few mononuclear inflammatory cells were encountered. At culture, Paecilomyces variotii, a common ubiquitous non-pathogenic saprophyte, was identified. Despite systemic, intravitreal and topical antifungal therapy after vitrectomy the uveitis recurred several times, but no fungal organisms were isolated from the repeat intraocular specimen. At 18 months postoperatively the subject's visual acuity was finger counting at 2 metres. At the time of surgery the operating room air-conditioning system was undergoing repairs. Cases of fungal endophthalmitis after contamination from air-conditioning ventilation systems have been reported before, but none of the cases reported have been caused by P. variotii. CONCLUSION: P. variotii, a non-pathogenic environmental saprophyte, may be disastrous if introduced into the eye. International recommendations on the environmental control of the operating room air-conditioning ventilation system should be strictly followed. No intraoperative surgery should be undertaken while the air-conditioning system is undergoing repairs or service.     

Heterologous Type I Collagen as an Add-on Therapy to Narrowband Ultraviolet B for the Treatment of Vitiligo: A Pilot Study

BackgroundThere is still an unsatisfied need for new treatments for vitiligo with more rapid onset and long-term sustainability of repigmentation.ObjectiveWe sought to evaluate the possible efficacy of heterologous type I collagen as an add-on therapy to narrowband ultraviolet B (NB-UVB) for the treatment of vitiligo.MethodsFive patients with non-segmental vitiligo older than 18 years with bilateral and approximately symmetrical vitiligo lesions that did not evolve in size for at least six months were included. All vitiligo lesions were treated with NB-UVB therapy according to the Vitiligo Working Group recommendations. Two selected nonfacial lesions of each patient were also treated with intradermal injections of heterologous type I collagen (HTIC) every two weeks. Repigmentation of HTIC plus NB-UVB-treated lesions and their symmetrical counterparts treated just with NB-UVB was evaluated at baseline and Week 12.ResultsRepigmentation of the HTIC-injected lesions started after the first treatment session in three cases and after the second session in two cases. After six sessions (Week 12), the mean repigmentation rate was 70.5 percent (95% confidence interval:0.569–0.841) in the NB-UVB plus HTIC treatment group versus 16.5 percent (95% confidence interval: 0.137–0.192) in NB-UVB treatment group (p=0.0006, paired t-test).ConclusionAlthough the number of patients treated with the combination treatment was limited in our study, our results suggest that the addition of HTIC to NB-UVB therapy might offer a more rapid onset of repigmentation in patients with vitiligo.     

The use of povidone‐iodine and sugar solution in surgical wound dehiscence in the head and neck following radio‐chemotherapy

Povidone‐iodine is known for successfully treating surgical wounds; the combination between povidone‐iodine and sugar, also called Knutson's formula, has been proposed to improve wound healing. Currently, no studies have investigated the effects of Knutson's formula to treat defects in wound closure following radio‐chemotherapy in the head and neck region. The aim of this study is to evaluate the efficacy of Knutson's formula in improving the wound‐healing process in patients who underwent radio‐chemotherapy after surgery for head and neck cancer. The study, conducted from August 2013 to January 2017, included a sample of 34 patients (25 males and 9 females; age range: 60‐75 years) treated with radio‐chemotherapy after head and neck cancer surgery. All patients suffered from defect of wound regeneration. Patients were randomly divided into two groups: patients in the study group (n = 18) were treated with Knutson's formula; patients in the control group (n = 16) were treated with traditional topical drugs. In the study group, 16 of 18 (88.9%) patients reached complete wound closure 1 month after treatment, with no wound infections. In the control group, only three patients (18.7%) showed complete wound closure within a month; in addition, one patient required systemic antibiotic treatment because of supra‐bacterial infection of the wound. In our sample, the combination of povidone‐iodine and sugar had a higher success rate compared with traditional topical treatment in the treatment of wound defect closure in oncological patients who underwent radio‐chemotherapy.     

Pulmonary embolism in pregnancy

Venous thromboembolism (VTE) is a major cause of maternal morbidity and mortality during pregnancy or early after delivery, remaining a diagnostic and therapeutic challenge in both states. The absolute incidence of pregnancy-associated VTE has been reported as 1 in 1,000 to 1 in 2,000 deliveries. With 5–6 million new births computed in Europe in 2010, the potential clinical relevance of diagnosing and treating gravidic VTE is immediately evident. Fivefold higher in a pregnant as compared with a non-pregnant woman, VTE risk is also higher in postpartum than antepartum period. Ranked absolute and relative thrombotic risk may be described in the several thrombophilic conditions experienced by women at risk, according to which specific prophylactic and therapeutic recommendations have been formulated by recent guidelines. The main purpose of the present review article was to emphasize the most recent findings and recommendations in diagnostic strategies, discussing thrombophilic risk evaluation, as well as risks and benefits of various diagnostic techniques for both mother and fetus.     

Recurrent small intestine intussusception in a patient with Peutz-Jeghers syndrome

Peutz-Jeghers syndrome is a rare hereditary autosomal dominant disease caused by a mutation of the tumor suppressor gene serine/threonine kinase 11 located in chromosome 19p13.3. It is characterized by the presence of extensive mucocutaneous pigmentation, especially of the lips and the occurrence of hamartomatous polyps throughout the gastrointestinal tract. Gastrointestinal hamartomas occur predominantly in the small intestine and can become symptomatic leading usually to intestinal obstruction and abdominal pain.We present a case of recurrent intestinal obstruction caused by small bowel intussusception treated by reduction, enterotomy and polypectomy and followed by intraoperative enteroscopy and endoscopic polypectomy.     

Constrictor prostanoids and uridine adenosine tetraphosphate: vascular mediators and therapeutic targets in hypertension and diabetes

Vascular dysfunction plays a pivotal role in the development of systemic complications associated with arterial hypertension and diabetes. The endothelium, or more specifically, various factors derived from endothelial cells tightly regulate vascular function, including vascular tone. In physiological conditions, there is a balance between endothelium-derived factors, that is, relaxing factors (endothelium-derived relaxing factors; EDRFs) and contracting factors (endothelium-derived contracting factors; EDCFs), which mediate vascular homeostasis. However, in disease states, such as diabetes and arterial hypertension, there is an imbalance between EDRF and EDCF, with a reduction of EDRF signalling and an increase of EDCF signalling. Among EDCFs, COX-derived vasoconstrictor prostanoids play an important role in the development of vascular dysfunction associated with hypertension and diabetes. Moreover, uridine adenosine tetraphosphate (Up₄A), identified as an EDCF in 2005, also modulates vascular function. However, the role of Up₄A in hypertension- and diabetes-associated vascular dysfunction is unclear. In the present review, we focused on experimental and clinical evidence that implicate these two EDCFs (vasoconstrictor prostanoids and Up₄A) in vascular dysfunction associated with hypertension and diabetes.