Total-body PET/CT using half-dose FDG and compared with conventional PET/CT using full-dose FDG in lung cancer.

PURPOSE: The purpose was to explore the effects of total-body PET/CT with half-dose 18F-FDG activity on image quality, compared with those of conventional PET/CT with clinical routine full-dose 18F-FDG in lung cancer. METHODS: Fifty-six primary lung cancer patients who underwent total-body PET/CT on a uEXPLORER scanner with half-dose (1.85 MBq/kg) 18F-FDG activity before treatment were retrospectively studied; among them, 28 patients were confirmed by postoperative pathologic examination and 28 patients by biopsy. After matching with the pathological study results, the other 28 patients with lung cancer who underwent surgery were selected for the full-dose (3.70 MBq/kg) group. Patients in the full-dose group were studied with a conventional uM780 PET/CT scanner. The acquisition time of the half-dose group was 15 min, split into 4-min and 2-min duration groups, which were all referred to as G15, G4 and G2, respectively. The PET/CT scanning speed in the full-dose group was 2 min/bed. Image quality was evaluated by subjective and objective analyses. The subjective analysis method was carried out with a 5-point scale (5-excellent, 1-poor). Objective analysis indicators of PET image quality included the SUVmax, SUVmean and signal-to-noise ratio (SNR) of the liver; the SUVmax and SUVmean of the blood pool; and the SUVmax and tumour-to-background ratio (TBR) of the lesions. G15 served as the reference for G2 and G4 to test lesion detectability. RESULTS: Image quality scores in G2 (4.3 ± 0.7) were significantly higher than those in the full-dose group (3.7 ± 0.6) (p = 0.004). The mean and SD of the image quality scores in G4 and G15 were 4.9 ± 0.2 and 5.0 ± 0.0, respectively. The liver SNR in G2 was significantly higher than that in the full-dose group; the corresponding SNR were 11.7 ± 1.5 and 8.3 ± 1.2 (p < 0.001), respectively. The liver SNR significantly increased with the time of acquisition among G2, G4 and G15 (11.1 ± 1.7, 15.2 ± 3.4 and 30.5 ± 6.0, all p < 0.05). G15 served as the reference, and all these lesions (100%) could be identified by G2 and G4. CONCLUSION: Total-body PET/CT with half-dose 18F-FDG activity in G2 and G4 achieved comparable image quality to conventional PET/CT, and its image quality was better than that of conventional PET/CT with clinical routine full-dose 18F-FDG in lung cancer.

Pharmacological management of cerebral venous sinus thrombosis with full-dose IV heparin infusion and its clinical outcomes.

OBJECTIVE: To report a case of successful use of unfractionated heparin (UFH) infusion to treat cerebral venous sinus thrombosis (CVST). CASE SUMMARY: A 54-year-old female with a history of ovarian cancer addressed through palliative care, presents to the Emergency Department complaining of nausea, vomiting and headache for the last 72h. The patient was on a home regimen of enoxaparin 1.5mg/kg subcutaneously daily for recent pulmonary embolism and deep vein thrombosis that developed while on warfarin therapy previously. CT scan showed superior sagittal sinus thrombosis. UFH infusion was initiated and continued for 48h until the headache dissipated. DISCUSSION: Stable CVST may be treated with UFH infusion; however, there is limited literature that describes UFH dosing for CVST management. CONCLUSIONS: UFH may be considered as one of the pharmacological agents to manage CVST. The dosing for UFH bolus and infusion is similar to treatment dose for pulmonary embolism/deep vein thrombosis management with goal anti-Xa between 0.3 and 0.7units/mL.

Is it necessary to treat mild asthmatic patients with the full dose treatment?

BACKGROUND: Routine protocol of asthma treatment has been focused on symptom suppression but severity of inflammation and spirometry findings may be neglected. We investigated the efficacy of full dose treatment protocol on patients with mild asthma symptoms with normal spirometry. MATERIALS AND METHODS: A before-after clinical trial study was conducted on patients with asthma symptoms (dyspnea, cough, and wheezing), while they had a near to normal pulmonary function test. Full dose treatment protocol (prednisolone 1 mg/kg for 5 days then fluticasone spray 250 mg four puffs daily plus salmeterol spray 25 mg four puffs daily), which was routinely used for severe asthma, was administrated and patients were followed up for 2 months. RESULTS: Sixty-eight patients (mean age (±SD) = 43.77 ± 10.70 years, female/male ratio; 47/53%) finally finished the study. At the baseline, mean forced expiratory volume in first second (FEV1) and forced vital capacity (FVC) were 91 ± 12% and 87 ± 11% of the predicted value, respectively. Two months after treatment, the mean FEV1 and FVC were 105 ± 14% and 97 ± 10%, respectively, which both improved compared with the baseline, significantly (P < 0.001). Frequencies of cough and dyspnea were significantly decreased (P = 0.041 and 0.034, respectively). CONCLUSION: Our result declared that full dose treatment can improve spirometry amounts and frequency of symptoms in patients with near to normal spirometry and obvious asthmatic symptoms. Routine treatment protocol of mild asthma recommends sole short-acting b2 receptor agonist, but it seems that pulmonary function and volume can be increased with more aggressive treatment.

Half dose ChAdOx1 nCoV-19 vaccine was equivalent to full doses to reduce moderate and severe COVID-19 cases.

Objectives: Previously, we presented the effectiveness of ChAdOx1 nCoV-19 half-dose (HD) immunization for preventing new COVID-19 cases. Here, we evaluated the administration of an HD of ChAdOx1 nCoV-19 in the primary immunization protocol (up to two doses) in reducing moderate and severe cases, hospitalizations, and deaths when compared to the administration of full doses (FD) after a long-term follow-up. Methods: We evaluated data from 29,469 participants between January 2021 and November 2022 who received an HD or FD vaccine and crossed this information with their medical records to identify those who developed moderate or severe cases. All participants were classified into four groups according to their immunization status and followed 500 days after the last vaccine administration. Results: The propensity-score matching analysis indicates that the administration of the two HDs of ChAdOx1 nCoV-19 was equivalent to the use of two FDs to reduce moderate and severe COVID-19 cases. The relative risk of being infected and developing moderate or severe conditions after the administration of at least one HD or FD was similar 150 or 500 days after the administration of the immunizers. Conclusion: Administering two HDs can be used safely as a cost-effective alternative to the primary immunization protocol.

Association of Incremental peritoneal dialysis with residual kidney function decline in patients on peritoneal dialysis: The balANZ trial.

BACKGROUND: Incremental peritoneal dialysis (PD), defined as less than Full-dose PD prescription, has several possible merits, including better preservation of residual kidney function (RKF), lower peritoneal glucose exposure and reduced risk of peritonitis. The aims of this study were to analyse the association of Incremental and Full-dose PD strategy with RKF and urine volume (UV) decline in patients commencing PD. METHODS: Incident PD patients who participated in the balANZ randomised controlled trial (RCT) (2004-2010) and had at least one post-baseline RKF and UV measurement was included in this study. Patients receiving <56 L/week and ≥56 L/week of PD fluid at PD commencement were classified as Incremental and Full-dose PD, respectively. An alternative cut-point of 42 L/week was used in a sensitivity analysis. The primary and secondary outcomes were changes in measured RKF and daily UV, respectively. RESULTS: The study included 154 patients (mean age 57.9 ± 14.1 years, 44% female, 34% diabetic, mean follow-up 19.5 ± 6.6 months). Incremental and Full-dose PD was commenced by 45 (29.2%) and 109 (70.8%) participants, respectively. RKF declined in the Incremental group from 7.9 ± 3.2 mL/min/1.73 m2 at baseline to 3.2 ± 2.9 mL/min/1.73 m2 at 24 months (p < 0.001), and in the Full-dose PD group from 7.3 ± 2.7 mL/min/1.73 m2 at baseline to 3.4 ± 2.8 mL/min/1.73 m2 at 24 months (p < 0.001). There was no difference in the slope of RKF decline between Incremental and Full-dose PD (p = 0.78). UV declined from 1.81 ± 0.73 L/day at baseline to 0.64 ± 0.63 L/day at 24 months in the Incremental PD group (p < 0.001) and from 1.38 ± 0.61 L/day to 0.71 ± 0.46 L/day in the Full-dose PD group (p < 0.001). There was no difference in the slope of UV decline between Incremental and Full-dose PD (p = 0.18). CONCLUSIONS: Compared with Full-dose PD start, Incremental PD start is associated with similar declines in RKF and UV.

Reduced- vs full-dose BCG in bladder cancer: A systematic review and meta-analysis.

OBJECTIVE: To assess the oncologic outcomes and the safety profile of a reduced-dose versus full-dose BCG regimen in patients with non-muscle-invasive bladder cancer (NMIBC). MATERIAL AND METHODS: We performed a systematic review according to Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA). The PubMed, Embase, and Web of Science databases were searched in January 2022 for studies that analyzed oncological outcomes and compared between reduced- and full-dose BCG regimens. RESULTS: Seventeen studies including 3757 patients met our inclusion criteria. Patients who received reduced-dose BCG had significantly higher recurrence rates (OR 1.19; 95%CI, 1.03-1.36; p = 0.02). The risks of progression to muscle-invasive BC (OR 1.04; 95%CI, 0.83-1.32; p = 0.71), metastasis (OR 0.82; 95%CI, 0.55-1.22; p = 0.32), death from BC (OR 0.80; 95%CI, 0.57-1.14; p = 0.22), and all-cause death (OR 0.82; 95%CI, 0.53-1.27; p = 0.37) were not statistically different. When restricting the analyses to randomized controlled trials, we found similar results. In subgroup analysis, reduced dose was associated with a higher rate of BC recurrence in studies that used only an induction regimen (OR 1.70; 95%CI, 1.19-2.42; p = 0.004), but not when a maintenance regimen was used (OR 1.07; 95%CI, 0.96-1.29; p = 0.17). Regarding side effects, the reduced-dose BCG regimen was associated with fewer episodes of fever (p = 0.003), and therapy discontinuation (p = 0.03). CONCLUSION: This review found no association between BCG dose and BC progression, metastasis, and mortality. There was an association between reduced dose and BC recurrence, which was no longer significant when a maintenance regimen was used. In times of BCG shortage, reduced-dose regimens could be offered to BC patients.

The progress of postapproval clinical studies on Sabin IPV.

As one of the powerful vaccines for completely eradicating all types of poliovirus in the polio endgame period, the novel IPV, which is prepared from attenuated polio Sabin strains (sIPV) and is expected to reduce the overall biosafety risk, was licensed in Japan (sIPV-containing diphtheria-tetanus-acellular pertussis combination vaccines, DTP-sIPV) and China (sIPV) in November 2012 and January 2015, respectively. Limited by the development progress and the manufactured sIPV ability, it has to date only been used in Chinese Expanded Programme on Immunization (EPI) by sequential scheduling with bOPV and in Japan with DTP-sIPV vaccination. We herein summarize postapproval clinical studies of sIPV in both full-dose schedules and sequential schedules, focusing on China, to evaluate sIPV safety and immunogenicity in large populations to provide important data for its broad application in developing countries worldwide.

Determinants of symptom burden related to bowel preparation for colonoscopy.

BACKGROUND: Symptoms developing during bowel preparation are major concerns among subjects who refuse the procedure. AIMS: We aimed to explore the determinants of symptoms occurring during preparation among patients undergoing elective colonoscopy. METHODS: This is a prospective multicenter study conducted in 10 Italian hospitals. A multidimensional approach collecting socio-demographic, clinical, psychological and occupational information before colonoscopy through validated instruments was used. Outcome was a four-category cumulative score based on symptoms occurring during preparation, according to the Mayo Clinic Bowel Prep Tolerability Questionnaire, weighted by intensity. Missing values were addressed through multiple imputation. Odds ratios (OR) and 95% confidence intervals (CI) were estimated through multivariate logistic regression models. RESULTS: 1137 subjects were enrolled. Severe symptoms were associated with female sex (OR=3.64, 95%CI 1.94-6.83), heavier working hours (OR=1.13, 95% CI=1.01-1.25), previous gastrointestinal symptoms (OR=7.81, 95% CI 2.36-25.8 for high score), somatic symptoms (OR=2.19, 95% CI=1.06-4.49 for multiple symptoms), day-before regimen (OR=2.71, 95%CI 1.28-5.73). On the other hand, age ≥60 years (OR=0.10, 95% CI 0.02-0.44) and good mood (p=0.042) were protective factors. A high-risk profile was identified, including women with low mood and somatic symptoms (OR=15.5, 95%CI 4.56-52.7). CONCLUSIONS: We identified previously unreported determinants of symptoms burdening bowel preparation and identified a particularly vulnerable phenotype. Symptoms during preparation especially impact heavier working activity.

Review of scientific evidence to support recommendations of the full-dose DTaP-IPV vaccination in pre-school age children in Italy.

INTRODUCTION: Two vaccine formulations are available to prevent diphtheria, tetanus, pertussis, and poliomyelitis: the pediatric full-dose (DTaP-IPV) and the reduced dose formulation (dTap-IPV). Different immunization schedules are internationally recommended for the pre-school booster dose. AREAS COVERED: International and Italian recommendations, scientific evidence on immunogenicity and safety of DTaP/dTap vaccines to support the full dose as a pre-school booster and Italian vaccination coverage (VC) up to adolescence. EXPERT OPINION: The WHO recommends a '3+1' schedule with DTaP vaccine for primary immunization, followed by a pre-school booster with DTaP or dTap vaccine. In Italy, a '2+1' schedule, with no booster in the second year, and a pre-school booster dose are recommended with DTPa-IPV vaccines. Studies showed a non-inferior immunogenicity in dTap vaccinees in pre-school age; nevertheless, the antibody titers were usually greater in children vaccinated with DTaP, while lower frequencies of adverse events were recorded in children receiving dTap. Italian VCs for pre-school and adolescent boosters have not been satisfactory, which further reduced during the COVID-19 period. In Italy, the pre-school booster offers the last chance to receive a full dose of DTaP vaccine, thus, representing the most suitable intervention to provide lasting protection in children.

[Efficacy of short-term full-dose prophylaxis in adult Chinese patients with severe hemophilia A].

OBJECTIVE: To investigate the efficacy of short-term full-dose prophylaxis in adult Chinese patients with severe hemophilia A. METHODS: Thirteen adult Chinese patients with severe hemophilia A receiving on-demand or low-dose prophylaxis underwent ultrasound examination of the target joints and evaluation of Hemophilia Joint Health Score (HJHS). The data of annual bleeding episodes in the period of on-demand or low-dose prophylaxis were collected retrospectively from the patients, and the changes in bleeding and joint condition (ultrasound findings of the target joints and HJHS) were observed during short-term full-dose prophylaxis. The activity intensity of the patients was assessed using the IPAQ questionnaire, and the 72 h FⅧ trough activity was measured during full-dose prophylaxis. RESULTS: The median age of the 13 patients was 26.0 (20.5-29.0) years. For full-dose prophylaxis, the patients received a median therapeutic dose of 31.0 (29.1-33.0) IU/kg, administered for 3 times per week; the median 72 h FⅧ trough activity of patients was 1.7% (1.3-3.4%). During the follow-up period for 3 months, the annual bleeding rates (ABR) and annual joint bleeding rates (AJBR) decreased significantly in all the patients (P=0.001 and 0.001, respectively), but zero bleeding was achieved in only 4 patients (30.8%) and zero joint bleeding in 7 patients (53.8%); 9 patients (69.2%) still experienced breakthrough bleeding. The damage severity of target joints assessed by ultrasound and HJHS in 6 patients (46.2%)was worse than before and no obvious progression of target joints damage was found in 7 patients (53.8%). Compared with the patients without progression, the patients with worsened joint damage had poorer baseline joint condition, higher bleeding frequencies before and during the follow-up, a higher intensity of physical activity, and a lower baseline FⅧ activity. CONCLUSIONS: At present, although short-term full-dose prophylaxis can significantly reduce the bleeding and partially prevent the progression of joint damage, it is not yet possible to achieve the goal of zero bleeding for all adult patients with severe hemophilia A in China, nor can it completely prevent further joint damage. For adult patients with different clinical bleeding phenotypes, joint conditions and physical activity intensity, individualized therapy involving additional evaluation methods should be implemented, and physiotherapy and surgical intervention can be considered when necessary.

Successful management of a patient with radiological presentation of choriocarcinoma syndrome before induction chemotherapy.

Choriocarcinoma syndrome is a life-threatening lysis syndrome caused by blood vessel rupture and subsequent tumor bleeding. We describe a case of pretreatment choriocarcinoma syndrome that developed in a 27-year-old man. He underwent a high orchiectomy at a local hospital and was diagnosed with metastatic testicular tumor given the high serum human chorionic gonadotropin levels (943,601 mIU/mL). Thus, he was referred to our institution. Although he had bulky lung metastases and alveolar bleeding, we were able to administer full-dose chemotherapy with etoposide and cisplatin. On day 3 of chemotherapy, he presented with severe hypoxia and worsening of alveolar bleeding. Thus, he underwent tracheal intubation at the Intensive Care Unit. Full-dose chemotherapy was continued, and the patient was extubated upon improvement. He is currently alive and continuing treatment at another hospital.

Evaluation of indications for reduced-dose non-vitamin K antagonist oral anticoagulants in hospitalised patients with atrial fibrillation.

BACKGROUND: Prevention of thromboembolic complications is a priority in patients with atrial fibrillation (AF). The use of non-vitamin K antagonist oral anticoagulants (NOACs) is more common and some patients have indications for a reduced dose. AIM: We sought to evaluate the frequency of NOACs being prescribed to AF patients and to compare the groups of AF patients receiving standard and reduced doses. METHODS: The study included 1327 patients diagnosed with AF and hospitalised at an institution of the highest referral level in cardiology in the years 2015-2016. Final analysis encompassed 713 patients with nonvalvular AF, who were prescribed NOACs upon discharge. RESULTS: In the group of patients receiving NOACs, standard doses were used in 383 (53.7%) patients, while 330 (46.3%) patients received reduced doses. Among patients treated with reduced doses, dabigatran was prescribed to 186 (56.4%) patients, rivaroxaban to 124 (37.5%) patients, and apixaban to 20 (6.1%) patients. Absence of indications for dose reduction was identified in 54 out of 330 (16.4%) patients receiving reduced-dose NOACs, including six out of 20 patients receiving reduced-dose apixaban (30%), 21 out of 186 patients receiving reduced-dose dabigatran (11.3%), and 24 out of 124 pa-tients receiving reduced-dose rivaroxaban (19.3%). Among patients treated with reduced dose of dabigatran (n = 186), one indication for dose reduction was observed in 75 patients, and at least two indications were observed in 90 patients. One indication was observed in 71 patients, and at least two indications were observed in 30 patients treated with a reduced dose of rivaroxaban (n = 124). CONCLUSIONS: Standard doses of NOACs were prescribed to most hospitalised AF patients. Apixaban was prescribed more frequently in the reduced-dose regimen, while the frequencies of standard and reduced doses prescribed were similar for dabigatran and rivaroxaban. Absence of indications for dose reduction as defined in relevant guidelines and Summaries of Product Characteristics was identified in 15.5% of patients receiving reduced doses of NOACs. More than one indication for dose reduction was identified in most patients receiving reduced-dose dabigatran, while one indication was identified in most patients receiving reduced-dose rivaroxaban.

Good Tolerance to Full-Dose Crizotinib in a Patient with Anaplastic Lymphoma Receptor Tyrosine Kinase-Rearranged Lung Adenocarcinoma and Preexisting Renal Impairment.

BACKGROUND: Crizotinib is an approved tyrosine kinase inhibitor in the treatment of advanced-stage non-small-cell lung cancer patients with anaplastic lymphoma receptor tyrosine kinase (ALK) rearrangement. Renal dysfunction after crizotinib administration was recently reported, but the physiopathological explanation and the safety in patients with preexisting renal dysfunction are still not clear. CASE PRESENTATION: A 44-year-old female and current smoker was diagnosed with a stage IV lung adenocarcinoma and treated with five lines of chemotherapy during a 4-year period of time. While she developed symptomatic tumor progression with deterioration of her performance status and renal dysfunction after these five lines of treatment, we discovered that her lung cancer was ALK-rearranged. We therefore proposed a treatment with full-dose crizotinib despite the renal impairment (creatinine clearance: 33 mL/min/1.73 m2) of unknown origin. A renal function worsening occurred after the initiation of crizotinib but we did not reduce the dose as recommended and this did not induce further deterioration. During the 15 months under crizotinib, the patient had a good general status, no clinically noticeable side effect, and a stable renal dysfunction, which even improved after the initial worsening and almost returned to the baseline (pre-crizotinib) status. CONCLUSION: This case report suggests that full-dose crizotinib may be continued even in patients with severe renal dysfunction and deterioration at treatment initiation, in parallel to careful follow-up of renal function and particular attention to avoid the use of concomitant nephrotoxic drugs.