Numerous Asymptomatic Brain Tuberculomas Complicated by Fatal Tuberculous Meningitis.

Tuberculosis (TB) is still one of the most challenging infectious diseases worldwide. Coinfection with HIV increases the likelihood of extrapulmonary involvement, including the tuberculosis of the central nervous system (CNS-TB). CNS-TB often presents as tuberculomas or tuberculous meningitis. Although tuberculomas can be single or multiple, asymptomatic carriage of numerous tuberculomas is seldom reported. We present a case of a 55-year-old man who carried at least 34 tuberculomas of different sizes asymptomatically before developing and succumbing to tuberculous meningitis. Furthermore, we highlight several possible public health challenges that might have complicated his clinical course, suggesting that future studies also focus on these variables alongside more traditional clinical issues.

Giant Basal Cell Carcinoma in a Renal Transplant Recipient: A Case Report.

Basal cell carcinoma is a skin cancer with a more benign clinical course, compared to other skin cancers. However, when left neglected, it can cause serious morbidity and mortality. A basal cell carcinoma larger than 5 cm is defined as giant. Common causes of these carcinomas are negligence, immunosuppression, low socioeconomic status, physical or mental dysfunction, light exposure, exposure to radiation, existence of a previous lesion, recurrence after treatment, and aggressive histologic pattern. In some cases, giant basal cell carcinoma has been described to infiltrate multiple intracranial structures and to be associated with distant metastasis. Herein, we present a case of a giant basal cell carcinoma on the temporary scalp of a renal transplant recipient with depression.

Use of Hepatitis C Virus Antibody-Positive Donors in Kidney Transplantation.

Background The use of kidney donors with hepatitis C virus (HCV) has been arising as a possibility to increase the donor pool. It encompasses both the use of donors with positive and negative viremia, particularly since the advent of direct antiviral agents that produce sustained virologic response. Methodology We conducted a retrospective observational study to describe the experience of our transplantation center in the use of HCV antibody-positive (HCV-Ab+) kidneys. Results We performed five transplants with HCV-Ab+ donors. The median age of kidney recipients was 63 (interquartile range (IQR) = 54-71) years, and 60% (n = 3) were males. Two recipients received a second transplant. The median dialysis vintage was 1,414 (IQR = 1,103-2,806) days. The induction immunosuppression protocol was basiliximab in most patients (60%, n = 3), and all received maintenance immunosuppression with tacrolimus, mycophenolate mofetil, and prednisolone. One of the recipients had a personal history of cured HCV infection. Seroconversion occurred in half of the remaining patients, which was sustained during the follow-up. None of the patients developed HCV viremia. At the end of follow-up, mean creatinine and proteinuria were 1.45 ± 1.12 mg/dL and 0.099 ± 0.045 g/g, respectively. We did not observe any rejection episodes, need for dialysis, or recipient's death. Conclusions Our work aligns with the current literature that advocates that the use of these donors is safe and cost-effective and can be an effective strategy for expanding the donor pool and augmenting the transplantation volume. Seroconversion is a known risk whose mechanisms are not entirely understood, although it does not appear to be related to a higher transmission risk.

Radiofrequency ablation plays double role in immunosuppression and activation of PBMCs in recurrent hepatocellular carcinoma.

Background: Radiofrequency ablation (RFA) is the primary curative treatment for hepatocellular carcinoma (HCC) patients who are not eligible for surgery. However, the effects of RFA on the global tumor immune response remain unclear. Method: In this study, we examined the phenotypic and functional changes in peripheral blood mononuclear cells (PBMCs) from recurrent HCC patients who had undergone two RFA treatments using mass cytometry and high-throughput mRNA assays. Results: We observed significant increase in monocytes and decrease in T cell subpopulations three days after the first RFA treatment and three days after the second RFA treatment. The down-regulation of GZMB, GZMH, GZMK, and CD8A, which are involved in the cytotoxic function of T cells, was observed following RFA. Furthermore, the population of CD8 effector and memory T cells (CD8 Teff and CD8 Tem) significantly decreased after RFA. The expression of CD5 and CD161 in various T cell subpopulations also showed significant reductions. Additionally, elevated secretion of VEGF was observed in monocytes, B cells, regulatory T cells (Tregs), and CD4 naive T cells. Conclusion: In recurrent HCC patients, serum components derived from radiofrequency therapy can enhance the antigen-presenting capacity of monocytes. However, they also inhibit the anti-cancer immune response by reducing the population of CD8 effector and memory T cells and suppressing the activation of T cells, as well as down-regulating the expression of CD161 and CD5 in various T cell subpopulations. These tumor-derived components also contribute to an immunosuppressive microenvironment by promoting the secretion of VEGF in monocytes, Tregs, B cells, and CD4 naive T cells.

Immune response to neurotoxic South American snake venoms.

South American rattlesnakes (Crotalus durissus spp) and coral snakes (Micrurus sp) venoms are characterized by inducing a limited inflammatory innate immune response, in contrast to Bothrops sp snake venoms which exert a prominent inflammatory activity. Some Crotalus durissus spp venoms, in addition, exert immunosuppressive activities that hamper the development of neutralizing antibodies in animals immunized for antivenom production. Micrurus sp venoms are rich in low molecular mass neurotoxins that elicit a limited immune response. These characteristics make it difficult to generate antivenoms of high neutralizing activity. Therefore, the study of the mechanisms operating behind this limited immune response to venoms is relevant from both fundamental and practical perspectives. This review summarizes key aspects of the immune response to these venoms and discusses some pending challenges to further understand these phenomena and to improve antivenom production.

An evidence-based review of optimal perioperative practices in minor hand surgery.

BACKGROUND: Like many surgical subspecialties, there have been frequent advancements and discoveries in the field of hand and upper extremity surgery. With a rapidly growing literature base, it can be difficult to remain updated on the latest recommendations. METHODS: A comprehensive literature search was completed on PubMed using MeSH terms. Topics included nutrition management, anticoagulation, immunosuppressive medication management, antibiotic use, skin preparation, splinting, tourniquet use, and suture choice. Data from articles with a level of evidence 1A-3 C were included. RESULTS: A total of 42 articles were identified and reviewed to provide evidence for recommendations regarding various aspects of pre-, intra-, and post-operative care. CONCLUSIONS: The objective of this manuscript is to serve as a resource for evidence-based recommendations by the findings of recent evidence related to perioperative care in elective hand surgery. Additional studies are required in certain areas of the literature in order to provide stronger recommendations.

The impact of COVID-19 on liver transplantation: challenges and perspectives.

The coronavirus disease 2019 (COVID-19) pandemic presented unique challenges to patients with decompensated cirrhosis awaiting transplant, with respect to accessing medical facilities for routine clinic visits, imaging, laboratory workup, or endoscopies. There was a delay in organ procurement that led to a decrease in the number of liver transplants (LTs) and an increase in the morality of waitlisted patients at the beginning of the pandemic. LT numbers later equalized to pre-pandemic numbers due to combined efforts and adaptability of transplant centers as well as dynamic guidelines. Due to being immunosuppressed, the demographics of LT patients were at an increased risk of infection. Although there is a higher rate of mortality and morbidity in patients with chronic liver disease, LT itself is not a risk factor for mortality in COVID-19. There was no difference in overall mortality in LT patients compared to non-LT patients, and mortality risk factors were the same: age, hypertension, diabetes, obesity, and chronic kidney disease. The most common causes of death were respiratory complications. Liver-related deaths were reported in 1.6% of patients. The optimal timing of liver transplantation post-infection depends on various factors, such as the severity of liver injury, the presence of comorbidities, and the progression of the underlying liver disease. There is not enough data available on COVID-19 cholangiopathy and the number of cases that will be seen in the future that will require LT. There are some concerns of lower immunogenicity of COVID-19 vaccines in LT patients but available evidence suggests that the vaccines are safe and well-tolerated.

The Complete Success in Refractory Mooren's Ulcer Treated with Infliximab.

PURPOSE: To describe the management and outcome of two extremely rare and painful cases of Mooren's ulcer, an idiopathic peripheral autoimmune-associated ulcerative corneal disease. METHODS: Case report with literature review on the management of ocular inflammation in Mooren's ulcer. RESULTS: A 47-year-old female and a 76-year-old female presented with progressive bilateral Mooren's ulcer that were refractory to conventional immunosuppressive therapy. Following treatment with infliximab, an anti-tumor necrosis factor alpha, a significant improvement in disease progression was observed, with no corneal thinning or perforation at follow-ups. CONCLUSION: This case report highlights how infliximab can be effective in cases with Mooren's ulcer refractory to conventional therapies.

Hypertrophic Perianal Herpes Mimicking Squamous Cell Cancer: A Case Report and a Review of the Literature.

Clinical practice frequently involves the discovery of perineal lesions. The human papillomavirus, molluscum contagiosum, and herpes simplex virus are to blame for the majority of these anogenital lesions. In the majority of cases, these lesions may be identified by their distinctive appearance. It is challenging to make a clinical diagnosis in immunocompromised people since these lesions might be large and have uncommon appearances. Verrucous perianal herpes is a rare type of herpes that resembles squamous cell carcinoma in gross appearance. We present a case of a 71-year-old man on azathioprine, an immunosuppressive drug for autoimmune pancreatitis, who developed a perianal lesion resembling squamous cell carcinoma. Excisional biopsy revealed a benign ulcerative lesion with herpetic inclusions. The patient received antiviral treatment, and the perianal wound completely healed. He developed a similar lesion in the perineum at one year follow up, which was successfully treated with oral and topical antivirals.

GPX1-associated prognostic signature predicts poor survival in patients with acute myeloid leukemia and involves in immunosuppression.

OBJECTIVE: Treatment of acute myeloid leukemia (AML) remains a challenge. It is urgent to understand the microenvironment to improve therapy and prognosis. METHODS: Bioinformatics methods were used to analyze transcription expression profile of AML patient samples with complete clinical information from UCSC Xena TCGA-AML datasets and validate with GEO datasets. Western blot, qPCR, RNAi and CCK8 assay were used to assay the effect of GPX1 expression on AML cell viability and the expression of genes of interest. RESULTS: Our analyses revealed that highly expressed GPX1 in AML patients links to unfavorable prognosis. GPX1 expression was positively associated with not only fraction levels of myeloid-derived suppressor cells (MDSCs), monocytes and T cell exhaustion, the expression levels of MDSC markers, MDSC-promoting CCR2 and immune inhibitory checkpoints (TIM3/Gal-9, SIRPα and VISTA), but also negatively with low fraction levels of CD4+ and CD8+ T cells. Silencing GPX1 expression reduced AML cell viability and CCR2 expression. Moreover, GPX1-targetd kinases were PKC family, SRC family, SYK and PAK1, which promote AML progression and the resistance to therapy. Furthermore, Additionally, GPX1-associated prognostic signature (GPS) is an independent risk factor with high area under curve (AUC) values of receiver operating characteristic (ROC) curves. High risk group based on GPS enriched not only with endocytosis which transfers mitochondria to favor AML cell survival in response to chemotherapy, but also NOTCH, WNT and TLR signaling which promote therapy resistance. CONCLUSION: Our results revealed the significant involvement of GPX1 in AML immunosuppression via and provided a prognostic signature for AML patients.

Are All Patients with Cancer at Heightened Risk for Severe Coronavirus Disease 2019 (COVID-19)?

Cancer patients are traditionally considered at high risk for complicated respiratory viral infections, due to their underlying immunosuppression. In line with this notion, early case series reported high mortality rates of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection in patients with malignancy. However, subsequent large, prospective, epidemiological surveys indicate that the risk for severe coronavirus disease 2019 (COVID-19) may be largely attributed to the multiple confounders operating in this highly heterogeneous population of patients, rather than the cancer or its treatment per se. We critically discuss the conundrums of SARS-CoV-2 infection in cancer patients and underscore mechanistic insights on the outcome of COVID-19 as it relates to cancer therapy and the type and status of the underlying malignancy. Not all cancer patients are similarly at risk for a complicated COVID-19 course. A roadmap is needed for translational and clinical research on COVID-19 in this challenging group of patients.

A Cannabinoid 2-Selective Agonist Inhibits Allogeneic Skin Graft Rejection In Vivo.

Previous work from our laboratory showed that a CB2 selective agonist, O-1966, blocked the proliferative response of C57BL/6 mouse spleen cells exposed to spleen cells of C3HeB/FeJ mice in vitro in the mixed lymphocyte reaction (MLR). The MLR is widely accepted as an in vitro correlate of in vivo grant rejection. Mechanisms of the immunosuppression induced by the cannabinoid were explored, and it was shown that O-1966 in this in vitro assay induced CD25+Foxp3+ Treg cells and IL-10, as well as down-regulated mRNA for CD40 and the nuclear form of the transcription factors NF-κB and NFAT in T-cells. The current studies tested the efficacy of O-1966 in prolonging skin grafts in vivo. Full thickness flank skin patches (1-cm2) from C3HeB/FeJ mice were grafted by suturing onto the back of C57BL/6 mice. O-1966 or vehicle was injected intraperitoneally into treated or control groups of animals beginning 1 h pre-op, and then every other day until 14 days post-op. Graft survival was scored based on necrosis and rejection. Treatment with 5 mg/kg of O-1966 prolonged mean graft survival time from 9 to 11 days. Spleens harvested from O-1966 treated mice were significantly smaller than those of vehicle control animals based on weight. Flow cytometry analysis of CD4+ spleen cells showed that O-1966 treated animals had almost a 3-fold increase in CD25+Foxp3+ Treg cells compared to controls. When dissociated spleen cells were placed in culture ex vivo and stimulated with C3HeB/FeJ cells in an MLR, the cells from the O-1966 treated mice were significantly suppressed in their proliferative response to the allogeneic cells. These results support CB2 selective agonists as a new class of compounds to prolong graft survival in transplant patients.

Design and evaluation of Taqman low density array for monitoring post-transplant viral infections.

BACKGROUND: The majority of transplant recipients undergo immunosuppressive treatment to prevent organ or tissue rejection. Consequently, they are more susceptible to infection agents including a number of viruses causing a significant morbidity and mortality. Only a limited number of viruses are currently tested for in transplant donors and recipients due to the cost and complexity. Taqman low density array (TLDA) may provide a suitable format to address more systematic testing approach. METHODS: One hundred and one liver transplant recipient samples were retrospectively tested for 48 viral targets including two controls (bovine viral diarrhea virus and MS2) and two common viruses (TTV and HPgV), using a custom designed TLDA. Eight samples were analysed simultaneously on 384-well TLDA. Samples giving a signal considered positive/indeterminant were re-tested by different individual confirmatory assays. RESULTS: Infections with six previously untested for viruses-EBV, HPIV3, HuPuV9, KIV, HMPV and HPV-were detected in fourteen patients. Previously detected HCV infections were also confirmed. These infections did not seem have an effect on 5 year post-transplant outcome. 55 of 79 and 17 of 87 samples available for confirmatory assays were positive for TTV and HPgV, included for the evaluation of the TLDA performance. CONCLUSIONS: The custom viral TLDA can be successfully used for simultaneous detection of a range of post-transplant viral infections. To fully exploit its potential for monitoring and intervention, a whole blood testing should be applied in a prospective setting.

Morbidity, perioperative outcomes and complications of robot-assisted radical prostatectomy in kidney transplant patients: A French multicentre study.

OBJECTIVE: Evaluate the safety, feasibility and efficiency of robot-assisted radical prostatectomy (RARP) in kidney transplant recipients, performed in high-volume French referral centres, and describe intra- and postoperative, oncological and functional outcomes. MATERIALS AND METHODS: A multicentre study was conducted on prospective RARP databases from 5 centres between 2008 and 2017. We retrospectively identified a first group (G1) of transplant patients. The following data were collected: age, body mass index, prostate-specific antigen, ISUP score, TNM stage, stratification according to d'Amico, renal function, renal disease, time between renal transplant and prostate cancer (PCa), operating time, bleeding, pre- and postoperative complications (according to Clavien). Group 1 data were matched with a second group (G2) of nontransplanted PTRA patients. RESULTS: A total of 321 patients were included (G1 N = 39 and G2 N = 282). The median operating time was 180 minutes (interquartile range 125-227) for G1 and 150 minutes (120-180) in G2 (P = 0.0623) and the median bleeding volume was 150 mL (150-400) and 250 mL (175-400), respectively (P = 0.1826). No grafts were damaged by RARP. Postoperative complication rate was significantly higher in G1: 51.2% vs. G2: 8.2% with a majority of minor complications (41%) according to Clavien Dindo (P < 0.001). Pathological assessment was as follows in G1: T2 = 28 (71.8%), T3 = 11 (28.2%), and G2: T2 = 206 (73.3%), T3 = 75 (26.7%) (P = 0.77). Postoperative ISUP scores were mainly grade 1: G1 = 14 (35.9%) vs. 99 (35.2%) in G2 and grade 2: respectively 18 (46.1%) 94 (33.5%). The rate of positive surgical margins was comparable in both groups: 13.2% for transplant patients vs. 18.1% (P = 0.65). Renal function was not significantly different at one year (P = 0.07). The median follow-up was 47.9 months (42.3; 52.5). CONCLUSION: RARP is conceivable to treat localized prostate cancer in kidney transplant recipients. This procedure does not appear to have any negative impact on graft renal function and cancer prognosis.

Can serum Procalcitonin aid in the diagnosis of blood stream infection in patients on immunosuppressive medications?

BACKGROUND: Patients on immunosuppressive medications may not exhibit the systemic inflammatory response syndrome (SIRS) in the setting of bacterial infection. Our study examines the relationship between serum PCT levels and the odds of manifesting SIRS and BSI in patients on immunosuppressive medications and examines whether this relationship is altered from patients who are not on these medications. The diagnostic performance of Procalcitonin (PCT) detecting BSI in patients on immunosuppressive agents is compared to that in non-immunosuppressed patients. METHODS: We tested the association between BSI, serum PCT levels, contemporaneous SIRS scores using logisitic regression in a dataset of 4279 patients. The diagnostic performance of these variables for detecting BSI was assessed. RESULTS: In patients on immunosuppressive medications, multivariate logistic regression models demonstrate that while the serum PCT level is associated with BSI (OR: 2.48, p < .05) - the SIRS score is not. At any given serum PCT level, patients on immunosuppressive agents have lower odds of exhibiting SIRS despite having the same odds of having BSI as non-immunosuppressed patients. PCT (AUC: 0.68) performs better than SIRS (AUC: 0.52) in detecting the presence of BSI in patients on immunosuppressive medications. The diagnostic performance of PCT for detecting BSI in immunosuppressed patients is not significantly different from the non-immunosuppressed cohort. CONCLUSIONS: As PCT levels rise, patients on immunosuppressive agents are less likely to mount a SIRS response, despite having a high probability of BSI. PCT might prove helpful in this setting as immunosuppressive agents do not alter the diagnostic performance of serum PCT in detecting BSI.

Implant treatment in pharmacologically immunosuppressed liver transplant patients: A prospective-controlled study.

OBJECTIVES: The main objective of this prospective study was to evaluate the long-term outcome of implant therapy in liver transplant patients (LTP). The secondary goal was to assess several implant- and patient-dependent variables, such as peri-implantitis (PI), peri-implant mucositis (PIM), bone loss (BL), and immediate postoperative complications. MATERIAL AND METHODS: Two groups, including 16 pharmacologically immunosuppressed LTP and 16 matched controls, received 52 and 54 implants, respectively, between 1999 and 2008. After evaluating the postoperative healing, a mean follow-up of more than 8 years was carried out, and radiographic, clinical, and periodontal parameters were recorded to evaluate implant survival and implant- and patient-dependent outcomes. RESULTS: The early postsurgical complications were similar in both groups. Implant survival rate was 100% in the LTP group and 98.15% in the CG. PIM was diagnosed in 35.42% of the implants and 64.29% of the patients of LTP group (LTPG) and in 43.40% of the implants and 56.25% of the patients in the CG. PI was detected in 4.17% of the implants and 7.10% of the patients in the LTPG and in 9.43% of the implants and 18.80% of the patients in the CG. CONCLUSION: Pharmacologically immunosuppression in liver transplant patients was not a risk factor for implant failure, nor for the incidence of peri-implant diseases. Liver transplant is not a contraindication for dental implant treatment, although these patients should be carefully monitored during follow-up care.

Efficacy of mycophenolate treatment in adults with steroid-dependent/frequently relapsing idiopathic nephrotic syndrome.

BACKGROUND: This study assessed the efficacy of therapy with mycophenolate (MF) and reduced doses of steroids in adults with steroid-dependent/frequently relapsing idiopathic nephrotic syndrome (SD/FR-INS). METHODS: Twenty-nine nephrotic patients (including 16 males and 13 females; mean age: 40 years, range: 18-74) were treated. Starting doses of MF were 2000 mg/day for mofetil MF (1500 mg/day in one patient) or 1440 mg/day for sodium MF. The initial prednisone (PDN) dose was 10 mg/day in 14 patients, 5 mg/day in two patients and no steroids in one patient. In the remaining 12 patients, moderate initial doses of PDN were administered (mean: 23.7 mg/day, range: 15-40), tapering to 10 mg/day after 1 month. RESULTS: Nephrotic syndrome remission was achieved in 27/29 cases (93.1%) (25 complete, 2 partial). Two patients showed resistance to the prescribed schedule. The first cycle of MF therapy was concluded in 20 patients after a mean (range) of 16.9 months (12-49). Maintenance of remission was observed in 11 of these 20 cases (55%) after a mean follow-up of 32.8 months (12-108). In nine patients with nephrotic syndrome relapse after tapering of MF (MF dependency), the same MF-PDN schedule was restarted, leading again to remission in all nine. The remaining seven MF-sensitive patients are still receiving their first therapeutic cycle. To date, the mean time under therapy in the 27 MF-sensitive patients is 38 months (4-216). Regarding complications, only minor digestive disorders and a slight decrease in blood haemoglobin levels were observed in a few patients. CONCLUSIONS: MF plus reduced doses of PDN is an effective and well-tolerated therapy for adult SD/FR-INS. Though MF dependence is observed, its low toxicity could allow long periods of therapy if it is required to maintain nephrotic syndrome remission.