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The article presents a case study of an 88-year-old woman who developed lichenoid drug eruption after administration of limaprost alfadex, a prostaglandin E1 (PGE1) derivative. Topics discussed include the performance of a lymphocyte stimulation test (LST), the use of oral methyl prednisolone and topical betamethasone butyrate propionate ointment for treatment, and the elevation of interleukin (IL)-17 production in patients with lichen planus.

The article presents a case study of an old woman with rheumatoid arthritis for five years. It discusses the results of her physical, laboratory and biochemical examinations. It notes that the patient showed a photoallergic drug eruption that is caused by certolizumab pegol which could be an initial step for sensitization and elicitation of the photoallergy.

The article presents a case study of CD30-positive cutaneous pseudolymphoma caused by tocilizumab, a biological disease-modifying anti-rheumatic drug (DMARD) that targets interleukin 6 (IL-6) receptor, blocking IL-6 signalling, in a 68-year-old woman patient. She was treated with topical patient was treated with topical betamethasone butyrate propionate ointment. The article discusses drug eruptions due to tocilizumab.

The article presents a case study of a 66-year-old woman with acute generalized exanthematous pustulosis (AGEP) caused by faropenem. Pruritic coalescent erythema and non-follicular pustules on her trunk and extremities were revealed through physical examination. It states that the case was the first report of drug eruption caused by faropenem.

The article describes a case study concerning a 71-year-old woman who died from toxic epidermal necrolysis (TEN) caused by the antibiotic cefozopran. Topics discussed include a widespread skin eruption after intravenous drug administration, the wide spread of erosions and scaly crusts on the chest, back and extremities, and the development of overwhelming septicemia and disseminated intravascular coagulation (DIC). Also mentioned are possible altered drug metabolism and immune mechanisms.

Urothelial carcinoma with histological variants is a clinically aggressive disease. We compared the clinical outcomes of urothelial carcinoma with histological variants to pure urothelial carcinoma in patients with advanced-stage bladder and upper urinary tract cancer receiving pembrolizumab after failure of platinum-based chemotherapy. The response of histological variants to pembrolizumab was not inferior to that of pure urothelial carcinoma. Introduction: Although variant urothelial carcinoma (VUC, defined here as urothelial carcinoma with any histological variant) is a clinically aggressive disease, the efficacy of pembrolizumab against VUC is not well characterized. This study assessed the therapeutic response and survival outcomes in patients with advanced VUC treated with pembrolizumab for unresectable recurrent or metastatic disease. Patients and Methods: We retrospectively evaluated 103 patients with advanced bladder and upper urinary tract cancer who received pembrolizumab after failure of platinum-based chemotherapy at 6 institutions between January 2018 and June 2021. Objective response rate (ORR), disease control rate (DCR), progression-free survival (PFS), and overall survival (OS) were compared between patients with pure urothelial carcinoma (PUC) and those with VUC. Results: We identified 81 and 22 patients with PUC and VUC, respectively. Squamous differentiation (n = 14) was the most common variant element, followed by glandular differentiation (n = 3) and micropapillary variant (n = 3). Baseline characteristics were comparable between the groups. Patients with VUC showed significantly better ORR (59.1% vs. 29.6%, P = .014) and comparable DCR (68.2% vs. 49.4%, P = .150) compared to those with PUC. There were no significant differences between the PUC and VUC groups with respect to PFS (median 5.0 months vs. 10.4 months, P = .222) or OS (median 13.5 months vs. 23.8 months, P = .497). Conclusion: Response of VUC to pembrolizumab was not inferior to that of PUC in patients with advanced-stage bladder and upper urinary tract cancer. [ABSTRACT FROM AUTHOR]

The coronavirus disease 2019 (COVID-19) vaccine is positively changing the health crises of this pandemic and is currently essential to overcome the COVID-19 pandemic. The vaccine shows high efficacy against the infection and impairs the severity of symptoms. However, this vaccination is associated with concerns, such as vaccine-associated adverse reactions, which are currently highlighted issues for clinicians. We experienced two cases of mild cutaneous adverse reaction following COVID-19 vaccine administration, which was successfully controlled by prior administration of the antihistamine agent fexofenadine 3 days before COVID-19 vaccination for 7 days. [ABSTRACT FROM AUTHOR]

Oxidized phospholipids have been shown to exhibit pleiotropic effects in numerous biological contexts. For example, 1-O-hexadecyl-2-azelaoyl-sn-glycero-3-phosphocholine (azPC), an oxidized phospholipid formed from alkyl phosphatidylcholines, is a peroxisome proliferator-activated receptor gamma (PPARγ) nuclear receptor agonist. Although it has been reported that PPARγ agonists including thiazolidinediones can induce plasma volume expansion by enhancing renal sodium and water retention, the role of azPC in renal transport functions is unknown. In the present study, we investigated the effect of azPC on renal proximal tubule (PT) transport using isolated PTs and kidney cortex tissues and also investigated the effect of azPC on renal sodium handling in vivo. We showed using a microperfusion technique that azPC rapidly stimulated Na+/HCO3 - cotransporter 1 (NBCe1) and luminal Na+/H+ exchanger (NHE) activities in a dose-dependent manner at submicromolar concentrations in isolated PTs from rats and humans. The rapid effects (within a few minutes) suggest that azPC activates NBCe1 and NHE via nongenomic signaling. The stimulatory effects were completely blocked by specific PPARγ antagonist GW9662, ERK kinase inhibitor PD98059, and CD36 inhibitor sulfosuccinimidyl oleate. Treatment with an siRNA against PPAR gamma completely blocked the stimulation of both NBCe1 and NHE by azPC. Moreover, azPC induced ERK phosphorylation in rat and human kidney cortex tissues, which were completely suppressed by GW9662 and PD98059 treatments. These results suggest that azPC stimulates renal PT sodium-coupled bicarbonate transport via a CD36/PPARγ/mitogen-activated protein/ERK kinase/ERK pathway. We conclude that the stimulatory effects of azPC on PT transport may be partially involved in volume expansion. [ABSTRACT FROM AUTHOR]

Immune checkpoint inhibitors (ICIs) have become the standard of care for the treatment of non-small cell lung cancer (NSCLC). With the increasing use of ICIs, clinicians should be familiar with their immune-related adverse events, including sarcoid-like reactions, which have been associated with the use of ICIs in patients with cancer. Sarcoid-like reactions are caused by uncontrolled T helper 1-mediated immune responses resulting from ICIs, but their pathophysiology is not fully understood. Sarcoid-like reactions are often clinically important because they mimic metastases from treated cancer. According to previous reports, sarcoid-like reactions are typically observed in intrathoracic locations (lung and/or mediastinal lymph nodes) and the skin. In this study, we report an extremely rare case of extrathoracic sarcoidlike reaction in the right external iliac lymph node following two cycles of pembrolizumab therapy in a patient with lung adenocarcinoma. The laboratory data and computed tomography images suggested that infectious and autoimmune diseases were not considered to be the causative agents. Residual bone metastasis might have caused T helper 1-mediated immune responses by pembrolizumab, and contributed to sarcoid-like reactions in the right external iliac lymph node. Sarcoid-like reactions should be considered in the differential diagnosis of patients with lung cancer treated with ICIs who exhibit worsening extrathoracic lymph node swelling. Clinicians should be cautious not to mistake extrathoracic sarcoid-like reactions of the lymph nodes for progression of the treated disease. [ABSTRACT FROM AUTHOR]

Enlarged bone metastasis from renal cell carcinoma (RCC) can cause skeletal-related events, and thus treatment to inhibit the growth of bone metastases is often required. Although radiotherapy for RCC bone metastases can achieve a certain degree of local control, evidence is lacking regarding the effects of systemic therapy to improve bone metastasis. The present study aimed to assess the treatment efficacy of targeted therapy and immune checkpoint inhibitors, and to determine whether systemic therapy without radiotherapy can shrink bone metastases of RCC. The present study retrospectively reviewed 44 patients with RCC with bone metastases treated via systemic therapy, including targeted therapy or immune checkpoint inhibitors. Patients were divided into two groups: Those who underwent systemic therapy with radiotherapy for bone lesions (n=29); and those who underwent systemic therapy without radiotherapy for bone lesions (n=15). The radiographical efficacy of systemic therapy and the time to progression of bone metastases were compared between groups. The overall response rate of systemic therapy with radiotherapy was 44%, and in total, 13 patients demonstrated a partial response. Only one patient (6%) had a partial response among those who were treated via systemic therapy without radiotherapy. The time to progression of bone metastasis was 9.5 and 2.1 months in patients treated with and without radiotherapy, respectively (P<0.0001). Collectively, the present results suggested that targeted therapy or immune checkpoint inhibitors without radiotherapy had only a slight effect on bone metastasis control. [ABSTRACT FROM AUTHOR]

Cisplatin-based systemic chemotherapy is the gold-standard approach for the first-line treatment of patients with advanced or metastatic urothelial carcinoma (UC). However, the optimal number of cycles is still unclear. The current study retrospectively assessed the clinical outcome in patients who received gemcitabine and cisplatin (GC) chemotherapy as first-line treatment for metastatic urothelial cancer to clarify the timing of switching from GC therapy. A total of 61 patients with locally advanced or metastatic UC who received first-line chemotherapy with GC were retrospectively reviewed at National Hospital Organization Kyushu Cancer Center between June 2009 and August 2017. The progression-free survival (PFS) and overall survival (OS) were evaluated using the Kaplan-Meier method. The significance of associations between the clinical parameters and OS was assessed using the Cox proportional hazards regression model. The median cycle number for GC chemotherapy was 4. The median PFS and OS of all cases was 5.2 and 14.1 months, respectively. The multivariate analyses revealed that a neutrophil-to-lymphocyte ratio ≥3.0 (hazard ratio [HR], 2.521, 95% confidence interval [CI]=1.179-5.624; P=0.017) and best response to GC therapy of CR+PR (HR 0.110; 95% CI=0.028-0.411; P<0.001) were independent prognostic factors. However, the number of GC cycles (≤4 vs. >4) was not an independent prognostic factor (P=0.387). The current retrospective study indicated that changes to therapy should be considered at an early stage for cases with a therapeutic effect of SD or less, regardless of the number of GC therapy cycles. [ABSTRACT FROM AUTHOR]

Most skin cancers develop as the result of UV light-induced DNA damage; however, a substantial number of cases appear to occur independently of UV damage. A causal link between UV-independent skin cancers and chronic inflammation has been suspected, although the precise mechanism underlying this association is unclear. Here, we have proposed that activation-induced cytidine deaminase (AID, encoded by AICDA) links chronic inflammation and skin cancer. We demonstrated that Tg mice expressing AID in the skin spontaneously developed skin squamous cell carcinoma with Hras and Trp53 mutations. Furthermore, genetic deletion of Aicda reduced tumor incidence in a murine model of chemical-induced skin carcinogenesis. AID was expressed in human primary keratinocytes in an inflammatory stimulus-dependent manner and was detectable in human skin cancers. Together, the results of this study indicate that inflammation-induced AID expression promotes skin cancer development independently of UV damage and suggest AID as a potential target for skin cancer therapeutics. [ABSTRACT FROM AUTHOR]

Dent's disease is an X-linked renal tubulopathy characterized by low molecular weight proteinuria, hypercalciuria and progressive renal failure. Disease aetiology is associated with mutations in the CLCN5 gene coding for the electrogenic 2Cl - /H + antiporter chloride channel 5 (CLC-5), which is expressed in the apical endosomes of renal proximal tubules with the vacuolar type H + -ATPase (V-ATPase). Initially identified as a member of the CLC family of Cl - channels, CLC-5 was presumed to provide Cl - shunt into the endosomal lumen to dissipate H + accumulation by V-ATPase, thereby facilitating efficient endosomal acidification. However, recent findings showing that CLC-5 is in fact not a Cl - channel but a 2Cl - /H + antiporter challenged this classical shunt model, leading to a renewed and intense debate on its physiological roles. Cl - accumulation via CLC-5 is predicted to play a critical role in endocytosis, as illustrated in mice carrying an artificial Cl - channel mutation E211A that developed defective endocytosis but normal endosomal acidification. Conversely, a recent functional analysis of a newly identified disease-causing Cl - channel mutation E211Q in a patient with typical Dent's disease confirmed the functional coupling between V-ATPase and CLC-5 in endosomal acidification, lending support to the classical shunt model. In this editorial, we will address the current recognition of the physiological role of CLC-5 with a specific focus on the functional coupling of V-ATPase and CLC-5., Competing Interests: Conflict-of-interest statement: The authors declare no conflict of interest related to this publication.

Infection is a common complication and is the second leading cause of death in hemodialysis patients. The risk of bacteremia in hemodialysis patients is 26-fold higher than in the general population, and 1/2-3/4 of the causative organisms of bacteremia in hemodialysis patients are Gram-positive bacteria. The ratio of resistant bacteria in hemodialysis patients compared to the general population is unclear. Several reports have indicated that hemodialysis patients have a higher risk of methicillin-resistant Staphylococcus aureus infection. The most common site of infection causing bacteremia is internal prostheses; the use of a hemodialysis catheter is the most important risk factor for bacteremia. Although antibiotic lock of hemodialysis catheters and topical antibiotic ointment can reduce catheter-related blood stream infection (CRBSI), their use should be limited to necessary cases because of the emergence of resistant organisms. Systemic antibiotic administration and catheter removal is recommended for treating CRBSI, although a study indicated the advantages of antibiotic lock and guidewire exchange of catheters over systemic antibiotic therapy. An infection control bundle recommended by the Center for Disease Control and Prevention succeeded in reducing bacteremia in hemodialysis patients with either a catheter or arteriovenous fistula. Appropriate infection control can reduce bacteremia in hemodialysis patients., Competing Interests: Conflict-of-interest statement: No conflicts of interest are associated with this article.

Renal proximal tubules (PTs) play important roles in the regulation of acid/base, plasma volume and blood pressure. Recent studies suggest that there are substantial species differences in the regulation of PT transport. For example, thiazolidinediones (TZDs) are widely used for the treatment of type 2 diabetes mellitus, but the use of TZDs is associated with fluid overload. In addition to the transcriptional enhancement of sodium transport in distal nephrons, TZDs rapidly stimulate PT sodium transport via a non-genomic mechanism depending on peroxisome proliferator activated receptor γ/Src/epidermal growth factor receptor (EGFR)/MEK/ERK. In mouse PTs, however, TZDs fail to stimulate PT transport probably due to constitutive activation of Src/EGFR/ERK pathway. This unique activation of Src/ERK may also affect the effect of high concentrations of insulin on mouse PT transport. On the other hand, the effect of angiotensin II (Ang II) on PT transport is known to be biphasic in rabbits, rats, and mice. However, Ang II induces a concentration-dependent, monophasic transport stimulation in human PTs. The contrasting responses to nitric oxide/guanosine 3',5'-cyclic monophosphate pathway may largely explain these different effects of Ang II on PT transport. In this review, we focus on the recent findings on the species differences in the regulation of PT transport, which may help understand the species-specific mechanisms underlying edema formation and/or hypertension occurrence.

Renal tubules regulate blood pressure and humoral homeostasis. Mediators that play a significant role in regulating the transport of solutes and water include angiotensin II (AngII) and nitric oxide (NO). AngIIcan significantly raise blood pressure via effects on the heart, vasculature, and renal tubules. AngII generally stimulates sodium reabsorption by triggering sodium and fluid retention in almost all segments of renal tubules. Stimulation of renal proximal tubule (PT) transport is thought to be essential for AngII-mediated hypertension. However, AngII has a biphasic effect on in vitro PT transport in mice, rats, and rabbits: stimulation at low concentrations and inhibition at high concentrations. On the other hand, NO is generally thought to inhibit renal tubular transport. In PTs, NO seems to be involved in the inhibitory effect of AngII. A recent study reports a surprising finding: AngII has a monophasic stimulatory effect on human PT transport. Detailed analysis of signalling mechanisms indicates that in contrast to other species, the human NO/guanosine 3',5'-cyclic monophosphate/extracellular signal-regulated kinase pathway seems to mediate this effect of Ang II on PT transport. In this review we will discuss recent progress in understanding the effects of AngII and NO on renal tubular transport.