OBJECTIVE: The effectiveness of mitomycin C (MMC) in trabeculectomy has long been established. The aim of this review is to evaluate the efficacy and safety of adjunctive agents in tube shunt drainage device surgery for glaucoma or ocular hypertension, since controversy still exists regarding their benefit.
METHODS: We searched CENTRAL, PubMed, Embase, Web of Science, Scopus, and BASE for RCTs, which have used adjuvant antimetabolites-either MMC or 5-Fluorouracil (5-FU)-and/or anti-vascular endothelial growth factors (anti-VEGF) agents. The main outcome was IOP reduction at 12 months.
RESULTS: Ten studies met our inclusion criteria. Nine used the Ahmed Glaucoma Valve (AGV) implant, while the double-plate Molteno implant was used in one study. Four studies used MMC. The remaining six studies used an anti-VEGF drug - either bevacizumab, ranibizumab or conbercept. Only one MMC-study reported a significant difference in the IOP reduction between groups at 12 months, favouring the MMC group (55% and 51%; p < 0.01). A significant difference was also reported by two out of five bevacizumab-studies, both favouring the bevacizumab group (55% and 51%, p < 0.05; 58% and 27%, p < 0.05), with the highest benefit seen in neovascular glaucoma cases, especially when panretinal photocoagulation (PRP) was also used. Neither ranibizumab nor conbercept were found to produce significant differences between groups regarding IOP reduction.
CONCLUSIONS: There is no high-quality evidence to support the use of MMC in tube shunt surgery. As for anti-VEGF agents, specifically bevacizumab, significant benefit seems to exist in neovascular glaucoma patients, especially if combined with PRP.

Recurrent IgA nephropathy (rIgAN) is an important cause of kidney allograft loss. Till now, no proven strategies have been confirmed to prevent/decrease the rIgAN. Here, a systematic review and meta-analysis were performed on the available interventions impacting rIgAN. PubMed, Embase, Web of sciences, ProQuest, and Cochrane library databases along with Google Scholar were searched for articles evaluating the rIgAN after kidney transplantation (up to 23 February 2023). The main inclusion criteria were kidney transplantation because of primary IgAN and articles studying the rate of the rIgAN based on different therapeutic interventions to find their effects on the disease recurrence. Based on our criteria, 11 papers were included in this systematic review, two of which pleased the criteria for the meta-analysis. Meta-analysis showed that the risk of the rIgAN in the steroid-free group was 3.33 times more than that of the steroid-receiving group (Pooled Hazard Ratio = 3.33, 95% CI 0.60 to18.33, Z-value = 1.38, p-value = 0.16). Steroid-free therapy increases the risk of rIgAN in kidney transplant recipients with primary IgAN. High-quality trials with large sample sizes studies are needed to confirm the impact of the steroids on decreasing the rate of the rIgAN.

Ginseng-containing traditional medicine preparations (G-TMPs) in combination with fluoropyrimidine-based chemotherapy (FBC) are well-known treatments for advanced gastric cancer (AGC), with a superior efficacy to FBC alone. However, evidence regarding their efficacy remains limited. The purpose of this meta-analysis is to evaluate the efficacy and safety of G-TMPs in combination with FBC for the treatment of AGC.
Eight electronic databases were searched for randomized controlled trials (RCTs) using G-TMPs with FBC for the treatment of AGC. The primary outcome included the tumor response, while the secondary outcomes included the quality of life (QoL), proportions of peripheral blood lymphocytes, adverse drug reactions (ADRs), and levels of cancer biomarkers. The quality of evidence for each outcome was assessed using GRADE profilers.
A total of 1,960 participants were involved in the 26 RCTs included. Patients treated with FBC plus G-TMPs had better objective response (risk ratio [RR] = 1.23, 95% confidence interval [CI]: 1.13 to 1.35, p < 0.00001) and disease control (RR = 1.13, 95% CI: 1.08 to 1.19, p < 0.00001) rates than those treated with FBC alone. Additionally, the combination group had a better QoL, higher proportions of CD3+ T cells, CD4+ T cells, and natural killer cells, as well as a higher CD4+/CD8+ T-cell ratio. Furthermore, lower levels of CA19-9, CA72-4, and CEA were confirmed in the combination treatment group. In addition, G-TMPs reduced the incidence of ADRs during chemotherapy.
In combination with FBC, G-TMPs can potentially enhance efficacy, reduce ADRs, and improve prognosis for patients with AGC. However, high-quality randomized studies remain warranted.
PROSPERO Number: CRD42021264938.

Fluoropyrimidine-based regimens have been investigated as the second line chemotherapy in patients with advanced pancreatic cancer refractory to gemcitabine. We conducted this systematic review and meta-analysis to evaluate the efficacy and safety profile of fluoropyrimidine combination therapy versus fluoropyrimidine monotherapy in such patients.
The databases of MEDLINE, EMBASE, Cochrane Central Register of Controlled Trials, ASCO Abstracts and ESMO Abstracts were systematically searched. Randomized controlled trials (RCTs) that compared fluoropyrimidine combination therapy versus fluoropyrimidine monotherapy in patients with gemcitabine-refractory advanced pancreatic cancer were included. The primary outcome was overall survival (OS). Secondary outcomes included progression-free survival (PFS), overall response rate (ORR) and serious toxicities. Statistical analyses were performed by using Review Manager 5.3. Egger\'s test was performed to assess the statistical evidence of publication bias by using stata 12.0.
A total of 1183 patients from six randomized controlled trials were included for this analysis. Fluoropyrimidine combination therapy increased ORR [RR 2.82 (1.83-4.33), p<0.00001] and PFS [HR 0.71 (0.62-0.82), p<0.00001], without significant heterogeneity. Fluoropyrimidine combination therapy improved OS [HR 0.82 (0.71-0.94), p = 0.006], with significant heterogeneity (I2 = 76%, p = 0.0009). The significant heterogeneity might have been caused by the different administration regimens and baseline characteristics. Peripheral neuropathy and diarrhea were more common in the regimens containing oxaliplatin and irinotecan, respectively. No publication bias was detected by Egger\'s tests.
Compared with fluoropyrimidine monotherapy, fluoropyrimidine combination therapy had a higher response rate and longer PFS in patients with gemcitabine-refractory advanced pancreatic cancer. Fluoropyrimidine combination therapy could be recommended in the second line setting. However, due to concerns about toxicities, the dose intensities of chemotherapy drugs should be carefully considered in patients with weakness.

Pterygium is an ultraviolet-related disease characterized by an aberrant, wing-shaped and active wound-healing process. There is nothing quite as disheartening for the surgeon or patient as the recurrence of pterygium, and various adjuvants have been studied to ameliorate this. This systematic review provides a comprehensive summary of the efficacy and safety of 5-Fluorouracil (5-FU) as an antimetabolite agent for pterygium management. An appraisal of electronic searches of six databases identified 34 clinical studies reporting recurrence outcomes of 5-FU use in primary, impending recurrent and recurrent pterygia. In vitro and in vivo studies of 5-FU showed dose- and duration-dependent cytostatic and cytotoxic effects in human cells. 5-FU is relatively inexpensive, available, and easy to administer, making it attractive for resource-limited scenarios. However, the published evidence demonstrates a recurrence rate of 11.4-60% with the bare scleral technique, 3.5-35.8% with conjunctival rotational flaps, 3.7-9.6% with conjunctival autografts for intraoperative topical 5-FU, and 14-35.8% for preoperative and intraoperative injections. This suboptimal efficacy brings the role of 5-FU as an adjuvant for pterygium surgery into question and the authors do not recommend its use. In contrast, postoperative intralesional injections of 5-FU to arrest progression in impending recurrent pterygium and true recurrent pterygia were more promising, with success rates of 87.2-100% and 75-100%, respectively. Furthermore, 5-FU as a treatment modality, without surgery, effectively arrested progression in 81.3-96% of primary and recurrent pterygia. Other treatments such as topical and intralesional corticosteroids, cyclosporine and anti-VEGF agents are discussed. Complications of 5-FU increase with higher doses and range from transient and reversible to severe and sight-threatening. For pterygium, 5-FU has a predilection for causing scleral thinning, corneal toxicity, and graft-related complications. Additional study with extended follow-up is needed to elucidate the optimal dose, frequency, duration, and long-term safety of 5-FU injections. If 5-FU is used in the management of pterygium, it should be with caution, in selected patients and with vigilant long-term monitoring.

Radiation recall dermatitis (RRD) is a skin reaction limited to an area of prior radiation triggered by the subsequent introduction of systemic therapy. To characterize RRD, we conducted a literature search, summarized RRD features, and compared the most common drug classes implicated in this phenomenon.
PubMed, Embase, Scopus, Web of Science, and Cochrane DBSR databases were queried through July 1, 2019 using key words: radiation recall, RRD, and radiodermatitis (limited to humans and English language). Studies included case reports in which patients treated with radiotherapy were initiated on a new line of systemic therapy and subsequently developed a skin reaction in the irradiated area. RRD cases were organized by whether RRD occurred after a single drug or multiple drug administration.
One-hundred fifteen studies representing 129 RRD cases (96 single-drug RRD, 33 multi-drug) were included. Sixty-three drugs were associated with RRD. Docetaxel (22) and gemcitabine (18) were the two drugs most commonly associated with RRD. Breast cancer (69 cases) was the most commonly associated tumor type. For single-drug RRD, the median radiotherapy dose was 45.0 Gy (range, 30.0-63.2 Gy). The median time from radiotherapy to drug exposure, time from drug exposure to RRD and time to significant improvement was 8 weeks (range, 2-132 weeks), 5 days (range, 2-56 days), and 14 days (range, 7-49 days), respectively. Variables significantly associated with grade ≥2 toxicity were docetaxel (P = 0.04) and non-antifolate antimetabolite (P = 0.05). The only variable significantly associated with grade ≥3 toxicity was capecitabine (P = 0.04).
RRD is a complex toxicity that can occur after a wide range of radiotherapy doses and many different systemic agents. Most commonly, it presents in patients diagnosed with breast cancer and after administration of a taxane or antimetabolite medication. RRD treatment generally consists of corticosteroids with consideration of antibiotics if superinfection is suspected. Drug re-challenge may be considered after RRD if the initial reaction was of mild intensity.

BACKGROUND: The benefit of loco-regional treatments such as hepatic arterial infusion (HAI) in terms of survival and response rate is unclear. The aim of this work is to quantitatively summarize the results of both randomized controlled trials (RCTs) and non-randomized studies of interventions (NRSIs) comparing fluoropyrimidine-HAI (F-HAI) to systemic chemotherapy (SCT) for the treatment of colorectal liver metastases (CRLMs).
METHODS: We searched the Cochrane Library, PubMed, EMBASE, and Web of Science up to July 1, 2021. The outcome measures were tumor response rate and overall survival (OS). Both RCTs and NRSIs comparing HAI to SCT for patients with unresectable CRLMs were included. The outcome measures were tumor response rate and OS. Two reviewers assessed trial quality and extracted data independently. All statistical analyses were performed using standard statistical procedures provided in Review Manager 5.2.
RESULTS: A total of 16 studies including 11 RCTs and 5 NRSIs were identified for the present meta-analysis. Nine RCTs compared F-HAI to SCT for patients with unresectable CRLMs and the pooled result indicated that patients who received F-HAI experienced more than twofold response rate than SCT, with a pooled risk ratio of 2.10 (95%CI 1.59-2.79; P < .00001). In addition, the pooled result based on RCTs showed that F-HAI had a significant benefit regarding OS, with a pooled HR of 0.83 (95% CI 0.70-0.99; P = .04). Similarly, the benefit of F-HAI in terms of OS was also observed in the results of NRSIs.
CONCLUSIONS: Our results indicated that the F-HAI regimen had a greater tumor response rate and survival advantage than SCT for patients with unresectable CRLMs. Future propensity score-matched analyses with a large sample size should be conducted to support the evidence of our results based on RCTs and NRSIs.

Gemcitabine is a commonly used antimetabolite that has been effective in a broad spectrum of tumors so far. The main grade three and four known toxicity of this drug is myelosuppression. Cardiac adverse events have rarely been reported and gemcitabine-induced atrial-fibrillation (AF) has been described in only five previous cases so far. Here we report the 6th case of gemcitabine-related AF. A 68-year-old man diagnosed with metastatic nasopharyngeal cancer was referred to our oncology department. He started first line chemotherapy with gemcitabine and cisplatin. He presented poorly tolerated atrial fibrillation related to gemcitabine infusion that lasted for six days. The treatment was then withdrawn and the patient received best supportive care. We conclude that Medical oncologists and cardiologists should be aware of such toxicities of gemcitabine, especially in the elderly who seem to be at a higher risk of such adverse events and which may dictate discontinuation of the drug.

Graft-versus-host disease (GvHD) was first described in 1959, since then major efforts have been made in order to understand its physiopathology and animal models have played a key role. Three steps, involving different pathways, have been recognised in either acute and chronic GvHD, identifying them as two distinct entities. In order to reduce GvHD incidence and severity, prophylactic measures were added to transplant protocols. The combination of a calcineurin inhibitor (CNI) plus an antimetabolite remains the standard of care. Better knowledge of GvHD pathophysiology has moved this field forward and nowadays different drugs are being used on a daily basis. Improving GvHD prophylaxis is a major goal as it would translate into less non-relapse mortality and better overall survival. As compared to CNI plus methotrexate the combination of CNI plus mycophenolate mophetil (MMF) allows us to obtain similar results in terms of GvHD incidence but a lower toxicity rate in terms of neutropenia or mucositis. The use of ATG has been related to a lower risk of acute and chronic GvHD in prospective randomized trials as well as the use of posttransplant Cyclophosphamide, with no or marginal impact on overall survival but with an improvement in GvHD-relapse free survival (GRFS). The use of sirolimus has been related to a lower risk of acute GvHD and significantly influenced overall survival in one prospective randomized trial. Other prospective trials have evaluated the use of receptors such as CCR5 or α4β7 to avoid T-cells trafficking into GvHD target organs, cytokine blockers or immune check point agonists. Also, epigenetic modifiers have shown promising results in phase II trials. Attention should be paid to graft-versus-leukemia, infections and immune recovery before bringing new prophylactic strategies to clinical practice. Although the list of novel agents for GvHD prophylaxis is growing, randomized trials are still lacking for many of them.

BACKGROUND: COVID-19 has been spreading worldwide with a significant death toll. Solid-organ transplantation (SOT) recipients are at higher risk due to their suppressed immune system. In this study, we aimed to conduct a systematic review on COVID-19 clinical manifestations and treatment strategies in SOT recipients.
METHODS: We searched three databases for relevant terms related to COVID-19 and transplantation. 50 studies, including 337 patients, were reviewed.
RESULTS: Two hundred thirty six patients were male, with a mean age of 49.9 years. The most prevalent group was the kidney 57.0%, followed by 17.2% heart and 13.6% liver. Fever and cough were the most reported clinical presentations. Infiltration (55.4%) in chest x-ray and ground-glass opacity (67.1%) in CT scans were the most radiological findings. It was found that 96.8% and 72.4% of patients present with CRP level and lymphocytopenia, respectively, and 70.6% of kidney recipients patients presented with high creatinine levels. The most common baseline immunosuppressants were calcineurin inhibitors (88.9%) and antimetabolites (73.2%). Antimetabolites (84.3%) and calcineurin inhibitors (54.3%) were discontinued/decreased 84.3% whereas glucocorticoids dosage almost has no change (77.9%) or even increased. 18.4% of cases had died, and 65.9% were discharged.
CONCLUSIONS: Patients\' demographics, signs, symptoms, and radiographic findings in SOT recipients are almost similar to the general population. However, gastrointestinal symptoms appear to be more common. There are different treatment strategies, but in most of them, antimetabolite and calcineurin inhibitors were decreased or discontinued, while corticosteroids were increased. Finally, COVID-19 seems to be more severe and has higher mortality in SOT recipients compared to the general population.