Fulminant Type 1 Diabetes Mellitus Caused by Long-Term Nivolumab Administration Followed by Nivolumab plus Cabozantinib Combination.

Nivolumab, an immune checkpoint inhibitor (ICI), is now used to treat many advanced cancers, including non-small cell lung cancer (NSCLC) and renal cancer. Immune-related adverse events are characteristic side effects of ICIs. Among them, fulminant type 1 diabetes mellitus is an infrequent but potentially life-threatening and clinically significant concern. Cabozantinib is known as a multikinase inhibitor. In recent years, combination therapy with nivolumab and cabozantinib has begun to be used to treat renal cell carcinoma. A 74-year-old man with no history of diabetes was treated with nivolumab for 5 years for NSCLC, followed by the combination of nivolumab and cabozantinib for clear cell renal cell carcinoma. He was diagnosed with fulminant type 1 diabetes 5 weeks after starting combination therapy, with symptoms of nausea and dry mouth. He was admitted to the intensive care unit and improved clinically with continuous insulin infusion and saline. The involvement of cabozantinib in the development of fulminant type 1 diabetes with long-term nivolumab use, which has not been reported previously, is unknown, but caution may be necessary in terms of glycemic control in combination therapy with nivolumab and cabozantinib.

A case of hypophosphatemia and elevated intact fibroblast growth factor 23 levels after short-term saccharated ferric oxide administration in a young woman and database analysis of adverse drug reactions in Japan.

Intravenous iron replacement therapy is a common treatment for iron deficiency. Commonly used agents in this treatment include ferric carboxymaltose, ferric derisomaltose, and saccharated ferric oxide (SFO). These drugs are known to elevate fibroblast growth factor 23 levels, resulting in hypophosphatemia, but in past reports, hypophosphatemia attributable to SFO treatment has been associated mainly with prolonged administration over several weeks. The present study details our experience of a case of moderate hypophosphatemia (<2 mg/dL) in a 22-year-old woman who had no specific history of hypophosphatemia during the first 5 days of SFO treatment, and showed an increase in intact fibroblast growth factor 23 levels within the first week of treatment. Cases of hypophosphatemia have been reported as occurring as early as 1 week after the start of SFO administration in the Japanese Adverse Drug Event Report database. These cases, along with our case, underline the need for awareness of the possibility of hypophosphatemia from the early stage of SFO administration, regardless of the patient's age or dosage, as well as the need to monitor patients to prevent complications.

Decubitus ulcer infection and bacteremia due to tazobactam/piperacillin-resistant Veillonella parvula.

This is the first case report of decubitus infection and bacteremia due to Veillonella parvula (V. parvula). A patient in his 70s with pre-existing diabetes mellitus was admitted with decubitus infection, and tazobactam/piperacillin treatment was initiated. Tazobactam/piperacillin-resistant V. parvula was detected in the blood and decubitus site cultures. The antimicrobial treatment was changed to clindamycin and cefmetazole. Antimicrobial therapy was administered for 28 days. The patient was transferred to a convalescent hospital. V. parvula occasionally causes infection in immunocompromised patients with underlying diseases, such as diabetes. An appropriate evaluation by culture test is important for diagnosis, treatment, and recurrence prevention. Tazobactam/piperacillin is often used in the treatment of multi-bacterial infections such as decubitus infections. V. parvula may be resistant to tazobactam/piperacillin, and this possibility should be taken into account when administering treatment.

Influence of Previous Therapy for Neutropenia Caused by Combination Therapy of Ramucirumab and Docetaxel.

In the present study, the influence of previous immune checkpoint inhibitor (ICI) therapy with ramucirumab (RAM) + docetaxel (DTX) therapy on the occurrence of severe neutropenia in patients with non-small cell lung cancer (NSCLC) was evaluated, taking into account the influences of cytotoxic chemotherapy used in pretreatment. The study participants included patients who received a combination therapy of RAM and DTX as cancer chemotherapy for NSCLC. The influences of previous ICI treatment and pretreatment with cytotoxic anticancer agents on the development of grade ≥ 3 neutropenia were analysed. A total of 89 patients, including 50 with and 39 without a history of ICI treatment, were analysed. Kaplan-Meier curves showed a significant difference in the influence of previous ICI treatment on the development of grade ≥ 3 neutropenia (p = 0.006). Moreover, Cox regression analysis identified a history of ICI treatment and prophylactic administration of G-CSF as factors associated with the development of grade ≥ 3 neutropenia (p = 0.018 and p < 0.001, respectively). This study found that previous treatment with ICIs reduced the incidence of grade ≥ 3 neutropenia after RAM + DTX therapy in patients with NSCLC, regardless of the influences of pretreatment with cytotoxic anticancer agents.

Successful pre-surgical treatment with carboplatin and gemcitabine chemotherapy for a patient with muscle-invasive bladder cancer and severe renal dysfunction.

Radical cystectomy is the standard treatment for muscle-invasive bladder cancer, and pre-surgical treatment can improve survival. Carboplatin and gemcitabine chemotherapy is considered an effective, safe treatment for patients ineligible for cisplatin-based chemotherapy owing to reduced renal function. However, there is limited evidence on pre-surgical treatment with carboplatin and gemcitabine chemotherapy with glomerular filtration rates < 30 mL/min. We discuss the treatment of a patient who did not undergo surgery owing to bladder tumor size of 12 cm (cT3bN0M1a) and severe renal dysfunction (serum creatinine: 2.57 mg/dL, estimated glomerular filtration rate: 20.2 mL/min/1.73 m2). After the patient received two courses of carboplatin and gemcitabine chemotherapy, the bladder tumor size had reduced by 60%. No nausea or renal dysfunction was observed; febrile neutropenia improved with antibiotic therapy and granulocyte colony-stimulating factor. Then, he could undergo robot-assisted radical cystectomy after the pre-surgical chemotherapy treatment. Pre-surgical treatment with carboplatin and gemcitabine chemotherapy is a viable treatment option for patients with muscle-invasive bladder cancer and severe renal dysfunction.

First Case Report of Peritoneal Dialysis-associated Peritonitis Caused by Lysinibacillus sphaericus.

We herein report a case of peritoneal dialysis-associated peritonitis caused by Lysinibacillus sphaericus in a 40s-year-old patient. Treatment was initiated with intermittent intraperitoneal cefazolin and ceftazidime. Later, both peritoneal dialysate and blood cultures detected L. sphaericus, so the antibiotic was changed to ampicillin (ABPC). The patient was treated with a combination of intraperitoneal intermittent and intravenous ABPC for 7 days, followed by 14 days of amoxicillin. The patient experienced no adverse events and no recurrence for 30 days. The patient had four dogs, and the infection was deemed likely to have been caused by environmental contamination and inadequate catheter replacement.

Two Cases of Exacerbation of Asthma during Treatment with Enfortumab Vedotin.

Enfortumab vedotin is an antibody-drug conjugate against nectin-4 that is recently being used in the management of patients with urothelial carcinoma. The common adverse events include rashes, peripheral neuropathy, and hyperglycemia. Only a few cases of associated respiratory symptoms have been reported. Herein, we describe 2 patients with advanced urothelial carcinoma who experienced asthma exacerbation after initiating enfortumab vedotin treatment. Both patients improved with inhalation therapy. Since nectin-4 is expressed in the tracheal epithelium, its association with asthma is likely. This study highlights that clinicians should caution patients with a history of asthma against the worsening of respiratory symptoms when enfortumab vedotin is administered.

A case of acute focal bacterial nephritis caused by methicillin-resistant Staphylococcus saprophyticus in a 13-year-old adolescent girl treated with daptomycin.

Staphylococcus saprophyticus is a gram-positive, coagulase-negative member of the Staphylococcus genus and is second only to Escherichia coli as a cause of urinary tract infections in the young female population. S. saprophyticus usually has good susceptibility to drugs commonly used to treat urinary tract infections, but it is often methicillin-resistant. Here we report a case of acute focal bacterial nephritis in a 13-year-old female patient caused by methicillin-resistant S. saprophyticus and treated with daptomycin (DAP). The patient had a history of unilateral hearing loss and presented to her previous physician with a 3-day history of fever, right-sided abdominal pain, and diarrhea. Cefotaxime antimicrobial chemotherapy was initiated as an empiric therapy targeting E. coli, the most frequent cause of community-onset pyelonephritis. Vancomycin (VCM) was started for acute focal bacterial nephritis caused by methicillin-resistant S. saprophyticus but was stopped due to allergy and replaced with DAP. After 13 days of treatment with DAP, the patient received 17 days of treatment with sulfamethoxazole-trimethoprim combination therapy. The patient experienced no adverse events and did not relapse. DAP is a relatively new anti-methicillin-resistant Staphylococcus aureus drug used to treat gram-positive cocci infections. It is primarily excreted by the kidneys, which may be desirable in treating urinary tract infections. For children who cannot receive VCM for any reason, DAP may be a viable alternative.

Fentanyl compared to buprenorphine for atrial fibrillation ablation analgesia and sedation: a retrospective cross-sectional study.

BACKGROUND: The effects of general anesthesia with deep sedation and conscious sedation have been compared for sedation management in the perioperative period for radiofrequency catheter ablation of the heart to treat atrial fibrillation. However, there is no consensus as to which drug to use for conscious sedation. This study aimed to investigate analgesic and sedative drugs suitable for perioperative ablation. METHODS: We retrospectively examined 93 patients who underwent atrial fibrillation ablation at Kariya Toyoda General Hospital between December 2017 and April 2019 and investigated differences in the outcomes, such as depth of sedation and postoperative adverse events between the buprenorphine hydrochloride (n = 46) and fentanyl citrate (n = 47) groups. RESULTS: The depth of sedation was similar between the two groups, without significant between-group differences in postoperative vomiting. The number of additional injections of thiamylal sodium to manage discomfort and pain during ablation were significantly lower in the fentanyl group. Additionally, the cumulative area product, cumulative total air kerma, 1-year postoperative atrial fibrillation recurrence rate, and postoperative complications were not significantly different between the two groups. CONCLUSIONS: Although there were no significant differences in the efficacy or safety between buprenorphine hydrochloride and fentanyl citrate as analgesics used during atrial fibrillation ablation, intraoperative body movements and patient discomfort could be reduced to a greater extent with the use of fentanyl.

[Incidence of taste disorder associated with cancer patients undergoing chemotherapy on an ambulatory basis].

Taste disorders are a common complaint among cancer patients undergoing chemotherapy on an ambulatory basis. We conducted a survey on the incidence of such disorders among 74 patients, and 45.95% (34 of 74 patients) developed taste disorders. When stratified by medication into a regimen including 5-FU and one including taxanes, taste disorders were found in 59.0% (23 of 39 patients) of the former and 60.0% (9 of 15) of the latter. The survey also included the effects of taste disorders on patients appetites. Both regimens led to reduced appetite in a number of these patients (39.1% and 44.4%, respectively). Among patients on the 5-FU-containing regimen, the FOLFOX/FOLFIRI therapy was found to be responsible for loss of appetite. Regarding change in tastes, many patients stated that the medication dulled their taste sensation except for bitterness; their capacity to sense intensity of taste remained unchanged. It was found that acute taste disorders develop frequently among patients on a high dosage of 5-FU or a taxane-containing regimen.

[Development of taste disorders following FOLFOX-FOLFIRI therapy and its effects on the QOL of patients with colorectal cancer].

Taste disorders are frequent occurrences among those patients under the FOLFOX-FOLFIRI regimen for colorectal cancer. We conducted a study on the development of taste disorders among colorectal cancer patients under this regimen and the effect of such disorders on their QOL. Taste disorders occurred in 58.1%(18/31 cases)of these patients and the disorders affected appetites in 50%(9 cases). The changes in taste sensations were subtle in most but some described certain tastes as exaggerated. Others reported changes in all taste sensations, including sweet, salty, bitter and sour, as well as deliciousness. When tested via the QOL Survey Sheet(Quality of Life Questionnaire for Cancer Patients Treated with Anticancer Drugs: QOL-ACD), the QOL was found to have deteriorated significantly in those who stated that taste disorders affected their appetite, in comparison with those who were unaffected. In patients with colorectal cancers and treated with the FOLFOX-FOLFIRI regimen, taste disorders are frequent occurrences. The poor nutritional state due to a loss of appetite may constitute a factor responsible for a lowering QOL.

[Prevention of oxaliplatin-related neurotoxicity by glutathione infusions].

We have used glutathione for prevention of oxaliplatin-related neurotoxicity with reference to the article of Cascinu et al. We investigated oxaliplatin-related neurotoxicity in Kariya Toyota General Hospital(KTGH)and compared with the data described in the article of Gamelin about the severity of its neurotoxicity. Grade 3 neurotoxicity was observed in only 5 of 44 patients(11.4%). The median number of cycles and cumulative dose of oxaliplatin were 12 cycles(5-27 / cycles)and 802.2(273.2-1,952.4)mg/m(2), respectively, at Grade 3 neuropathy. We evaluated retrospectively neuro-toxicity grade at cumulative oxaliplatin doses of approximately 500-520 mg/m(2). The severity of neurotoxicity observed in KTGH was significantly lower than in the group without Ca/Mg. We found no difference between the group with glutathione and / with Ca/Mg. Glutathione infusions seemed to prevent oxaliplatin-related neurotoxicity.

Effect of chitosan film containing basic fibroblast growth factor on wound healing in genetically diabetic mice.

Basic fibroblast growth factor (bFGF) has been shown to stimulate wound healing. However, consistent delivery of bFGF has been problematic. We studied the stability of bFGF incorporated into a chitosan film as a delivery vehicle for providing sustained release of bFGF. The therapeutic effect of this system on wound healing in genetically diabetic mice was determined as a model for treating clinically impaired wound healing. A chitosan film was prepared by freeze-drying hydroxypropylchitosan (a water-soluble derivative of chitosan) acetate buffer solution. Growth factor was incorporated into films before drying by mixing bFGF solution with the hydroxypropylchitosan solution. bFGF activity remained stable for 21 days at 5 degrees C, and 86.2% of activity remained with storage at 25 degrees C. Full-thickness wounds were created on the backs of diabetic mice, and chitosan film or bFGF-chitosan film was applied to the wound. The wound was smaller in after 5 days in both groups, but the wound was smaller on day 20 only in the bFGF-chitosan group. Proliferation of fibroblasts and an increase in the number of capillaries were observed in both groups, but granulation tissue was more abundant in the bFGF-chitosan group. These results suggest that chitosan itself facilitates wound repair and that bFGF incorporated into chitosan film is a stabile delivery vehicle for accelerating wound healing.