Comparative evaluation of intranasal midazolam-ketamine, dexmedetomidine-ketamine, midazolam-fentanyl, and dexmedetomidine-fentanyl combinations for procedural sedation and analgesia in pediatric dental patients: a randomized controlled trial.

Background: In order to assess the effectiveness of various analgesio-sedative combinations for pain relief and sedation in pediatric dental patients, a thorough evaluation of clinical studies and patient outcomes is necessary. Methods: A total of 128 healthy, uncooperative pediatric dental patients were randomly allocated to receive one of the four combinations of drugs via the intranasal (IN) route: Group I received midazolam-ketamine (MK), Group II received dexmedetomidine-ketamine (DK), Group III received midazolam-fentanyl (MF), and Group IV received dexmedetomidine-fentanyl (DF) in a parallel-arm study design. The efficacy and safety of the combinations were evaluated using different parameters. Results: The onset of sedation was significantly faster in the DF group than in the DK, MF, and MK groups (P < 0.001). The depth of sedation was significantly higher in the DK and DF groups than in the MK and MF groups (P < 0.01). DK and DF produced significant intra- and postoperative analgesia when compared with combinations of MK and MF. No significant adverse events were observed for any of the combinations. Conclusions: The DK and DF groups showed potential as analgesio-sedatives in view of their anxiolytic and analgesic effects.

Non-surgical management of a large periapical lesion with internal resorption using PRF, hydroxyapatite and MTA.

Periapical lesions of endodontic origin are caused by microbial infection of pulp. According to various studies, it is known that necrosis of pulp provides a favourable habitat for microbes to replicate and release various toxins into the periapical tissue leading to inflammation and formation of a periapical lesion. A variety of non-invasive methods to manage such lesions include conservative root canal treatment, aspiration-irrigation technique, decompression technique, calcium hydroxide therapy, lesion sterilisation and tissue repair therapy, and the apexum procedure. We present a case report describing non-surgical management of a large periapical lesion associated with a permanent central incisor displaying internal inflammatory resorption using platelet rich fibrin (PRF), bone graft and mineral trioxide aggregate (MTA).

Feasibility and Compatibility of Minilaparotomy Hysterectomy in a Low-Resource Setting.

INTRODUCTION: Minilaparotomy hysterectomy (MLH) relies on the simplicity of the traditional open technique of abdominal hysterectomy, imparts cosmesis and faster recovery of laparoscopic hysterectomy yet avoids the long learning curve and cost of expensive setup and instrumentation associated with the minimally invasive approaches, namely, laparoscopy and robotics. In the present study, we tried to ascertain whether the results obtained with MLH can be compared to LAVH in terms of its feasibility, intraoperative variables, and complications. The null hypothesis was that both MLH and LAVH are comparable techniques; thus, where cost and surgeon's experience are the confining issues, patients can be reassured that MLH gives comparable results. MATERIALS AND METHODS: This was a prospective observational study done over a period of two years at a university teaching hospital. A total of 65 patients were recruited, but only 52 (MLH: 27; LAVH: 25) could be included in final analysis. All surgeries were performed by one of the two gynecologists with almost equal surgical competence, and outcomes were compared. RESULTS: MLH is a feasible option for benign gynecological pathologies as none of the patients required increase in the initial incision (4-6 cm). MLH could be done for larger uteri (MLH: 501.30 ± 327.96 g versus LAVH: 216.60 ± 160.01 g; p < 0.001), in shorter duration (MLH: 115.00 ± 21.43 min versus LAVH 172.00 ± 27.91 min; p < 0.001), with comparable blood loss (MLH: 354.63 ±227.96 ml; LAVH: 402.40 ± 224.02 ml; p=0.334), without serious complications when compared to LAVH. CONCLUSION: The technique of MLH should be mastered and encouraged to be used in low-resource setting to get results comparable to laparoscopic surgery. This trial is registered with NCT03548831.

Serum Th1 and Th2 cytokine balance in patients of superficial transitional cell carcinoma of bladder pre- and post-intravesical combination immunotherapy.

Combination therapy with intravesical bacillus Calmette-Guerin (BCG) plus interferon-alpha2b (IFN-alpha2b) for superficial transitional cell carcinoma (TCC) seems to be immune-dependent and activation of Th1 immune response is required for clinical efficacy. The present study evaluates circulating serum cytokine profiles (Th1/Th2 cytokines IFN-gamma, IL-2 TNF-alpha, IL-4, IL-6 and IL-10) in 41 bladder cancer patients prior to transurethral resection of tumor (TURBT) (pre-therapy), and following intravesical combination immunotherapy (post-therapy) and their association with recurrence. Mean levels of IL-2 and TNF-alpha were significantly reduced while IL-4, IL-6 and IL-10 were significantly enhanced in pre-therapy samples as compared to controls. Mean levels of IFN-gamma, IL-2 and TNF-alpha were significantly increased while IL-4 and IL-10 were significantly reduced in patients after instillation of combination immunotherapy. These findings suggest that bladder cancer patients develop Th2 dominant status with deficient type 1 immune response that shows tendency to reversal following therapy.

Ex vivo triggering of T-cell-mediated immune responses by autologous tumor cell vaccine in oral cancer patients.

We investigated immunomodulatory activity of autologous tumor cell vaccine from oral cancer patients ex vivo by lymphoproliferation assay and two color flow cytometry. Vaccine treatment lead to 10-fold higher proliferation of lymphocytes compared with the untreated controls. A significant increase in CD69(+) and HLA-DR(+) T-cells was observed in vaccine pulsed cultures compared with untreated (p<0.0001) controls. The frequency of IFN-gamma and IL-2 expressing CD4(+)/CD8(+)T-cell subsets was significantly higher with a concomitant reduction in IL-4 and IL-10 expression in the vaccine-treated group (p<0.0001) compared with the untreated controls. Vaccine treatment further increased T-cell receptor Vbeta3, Vbeta5, and Vbeta8 usage. It seems that the autologous tumor cell vaccine triggers T-cell responses ex vivo, hence it may have a protective role in oral cancer patients.

Adjuvant intravesical therapy based on an in vitro cytotoxicity assay in the management of superficial transitional cell cancer of the urinary bladder.

OBJECTIVE: To investigate the utility of an individualized chemo/immunotherapy regimen of intravesical therapy based on the results of an assessment of in vitro cytotoxicity. PATIENTS AND METHODS: Intravesical adjuvant chemo/immunotherapy was given to 47 patients based on the results of in vitro cytotoxicity assay of the responses of cultured autologous tumour cells to various cytotoxic drugs (mitomycin-C, doxorubicin and cisplatin) and immunomodulating agents (bacillus Calmette-Guérin, BCG and interferon-alpha2b). Intravesical therapy was given as single- or double-drug regimens according to the assay results: 16 (34%) patients showed cytotoxicity to a single drug and 31 (66%) showed maximum cytotoxicity to a combination of immunomodulators and cytotoxic agents. The efficacy of treatment in terms of tumour-free survival and recurrence rate was compared with 40 patients receiving intravesical BCG according to International Protocol (control group). RESULTS: In the in vitro assay group, seven patients (15%) had tumour recurrence, compared to 15 (38%) in the control group (P = 0.02). In the in vitro group, one of 16 patients on a single drug and six on the double-drug regimen had a recurrence. The patients given BCG with cytotoxic drugs had no recurrences, but 29% of patients given interferon-alpha2b combinations had recurrences. Kaplan-Meier analysis showed a longer recurrence-free survival in the in vitro group (75%) than in the control group (49%) at 48 months of follow-up. CONCLUSION: Intravesical therapy based on an in vitro cytotoxicity assay is an attempt to give individualized therapy, and to increase tumour-free survival in these patients, with no side-effects. Recurrences in seven patients in the in vitro group might be due to a defective host immune response, or to expansion of a subclone of tumour cells resistant to all treatment.