Rhabdomyolysis Caused by Gefitinib Overdose

Epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors (TKIs) are common therapeutic agents for EGFR mutation-positive advanced non-small-cell lung cancer. There has been no report of rhabdomyolysis caused by an overdose of EGFR-TKIs. We herein review the existing literature on the subject and report a rare case of rhabdomyolysis due to an overdose of gefitinib, an EGFR-TKI.     

Safe Concurrent Use of Anti-tuberculosis Drugs and Pembrolizumab in a Patient with Non-small-cell Lung Cancer Who Was Infected with Mycobacterium tuberculosis

A 68-year-old Japanese man was diagnosed with lung adenocarcinoma stage IVB. We introduced a first-line chemotherapy of four cycles of carboplatin and pemetrexed and pembrolizumab, followed by pemetrexed and pembrolizumab maintenance therapy. Approximately four months after anticancer therapy, a small nodule appeared in the right peripheral S3 lesion. After five months, the nodule was confirmed as a Mycobacterium tuberculosis (TB) nodule. We initiated anti-TB therapy without stopping pembrolizumab, and the right S3 nodule shrank immediately. This report supports the concurrent use of anti-TB treatment with an immune checkpoint inhibitor when the TB infection area is limited.     

Severe Post-COVID-19 Organizing Pneumonia during Cancer Immunochemotherapy

A 44-year-old man developed coronavirus disease 2019 (COVID-19) pneumonia during immunochemotherapy consisting of carboplatin, paclitaxel, and pembrolizumab for non-small cell lung cancer. Low-grade fever, followed by mild hypoxemia, and febrile neutropenia, were observed, and granulocyte colony-stimulating factor (G-CSF) was administered until the recovery of neutropenia, when he developed a high fever, severe hypoxemia, and hypotension accompanied by consolidation in the bilateral lungs. His conditions promptly improved after treatment including hydrocortisone and the primary and metastatic tumors remained regressed for 10 months without further treatment. Post-COVID-19 organizing pneumonia during cancer immunochemotherapy can be aggravated by immune-checkpoint inhibitors and G-CSF.     

Effect of Dietary Fibre on Urinary Thiamin Excretion in Humans

The process of red sorghum malt production was monitored three times in five production units (PU) selected upon their ability to produce malt flours having a high capacity to fluidify high-energy-density gruels. Raw, germinated and degermed seeds were analysed for macronutrient, soluble sugars, phytate and cyanide contents and α-amylase activity. Know-how differences between producers lay mainly in the duration and type of equipment used for steeping and germination. Moreover, three PUs applied a maturation step before sun-drying and one PU added ashes to steeped seeds before germination. No significant difference was detected in the proximate composition of malts from the five PUs. For all PUs, traditional malting increased the protein content and decreased the lipid and ash contents, while the fibre content was not affected. Significant increases in sugar contents and in α-amylase activity were observed but in variable proportions from one PU to another. The phytate content decreased significantly in all PUs. The cyanide content increased in all PUs but more drastically or less drastically according to the PU. Finally, degerming lowered the cyanide content to an acceptable level for human consumption. The between-PU variability may be due either to the nature and origin of the raw seeds or to technological know-how differences between producers. Further investigations are needed to optimize and standardize the malting process with a view to maximizing α-amylase and phytase activities and minimizing the variability of their biochemical characteristics.     

Staged Fontan procedure for mitral atresia associated with severe tricuspid regurgitation, pulmonary hypertension, and pulmonary artery distortion

Optimal initial palliation and a subsequent staged approach is mandatory for high-risk Fontan candidates. We describe the case of mitral atresia with severe tricuspid regurgitation and pulmonary hypertension successfully managed by repeated palliation from the neonatal period and 2-stage Fontan surgery. A 1-month-old boy diagnosed with mitral atresia and double-outlet right ventricle underwent pulmonary artery banding at 1 month of age, followed by repeated pulmonary artery banding accompanied by tricuspid annuloplasty and atrial septal defect enlargement at 6 months. Because of the presence of pulmonary artery distortion, right ventricular dysfunction, and borderline pulmonary vascular resistance, a hemi-Fontan procedure was conducted with extended pulmonary artery plasty when the boy was 3 years and 8 months old. Cardiac catheterization done 3 months after showed improvement in risk factors, and the final Fontan operation (total cavopulmonary connection) was successfully done in conjunction with repeated tricuspid annuloplasty when the boy was 4 years and 5 months old. The patient remains in excellent clinical condition at the last follow-up 5 years after the final Fontan procedure with sinus rhythm and good ventricular function.     

Voriconazole-associated salt-losing nephropathy

A 74-year-old man was diagnosed with nephrotic syndrome due to focal segmental glomerulosclerosis, and steroid therapy was initiated. Subsequently, he was affected by deep mycosis, and hence, voriconazole (VRCZ) was administered. On the 16th day, he was transferred to our hospital because of somnolence and malaise. His systolic blood pressure was approximately 80 mmHg, and he showed decreased skin turgor, indicating volume depletion. Laboratory analysis revealed hyponatremia and liver dysfunction. Discontinuation of VRCZ and drip infusion of normal saline improved the consciousness disorder, hyponatremia, and liver dysfunction. The levels of antidiuretic hormone (ADH) and plasma renin activity were elevated. This patient showed high excreted urine sodium, despite volume depletion and low serum osmolality. Therefore, this patient was diagnosed with salt-losing nephropathy (SLN). SLN should be considered for treatment of VRCZ-associated hyponatremia, together with syndrome of inappropriate secretion of ADH.     

Host affinity and phylogenetic position of a new anamorphic fungus Beltraniella botryospora from living and fallen leaves of evergreen oaks

A new anamorphic fungus, Beltraniella botryospora, is described and illustrated with line drawings and photographs. This fungus was isolated frequently from living and fallen leaves of Quercus acuta, but rarely or never from other evergreen oaks and Castanopsis sieboldii grown at the same investigation site, suggesting that this new fungus might have strong host affinity to Quercus acuta. The phylogenetic relationships of Beltraniella botryospora and allied beltranioid fungi, such as Beltrania rhombica, Beltraniella sp. and Beltraniopsis sp., were estimated by molecular phylogenetic analysis using 28S rDNA D1/D2 region sequences. The constructed phylogenetic tree suggests that beltranioid fungi, including Beltraniella botryospora, an ascomycete Pseudomassaria carolinensis, which has a Beltraniella anamorphic stage, and a hyphomycete Subramaniomyces fusisaprophyticus, make a monophyletic group. This clade is located in the Xylariales lineage and is closely related to Amphisphaeriaceae. The phylogenetic relationships of the new anamorphic species and allied fungi are briefly discussed and a polyphyly of the anamorphic genus Beltraniella is suggested.     

NK1 receptor activation by geniohyoid primary afferents modulates parasympathetic postganglionic neuronal excitability in the rat

Brain activation patterns derived from neurofunctional methods are often implicitly regarded as being directly related to subjective perceptual experience in an iso- or at least homomorph manner, neglecting the operational differences between these two dimensions. This paper (a) introduces a method for assessing 'perceptual maps' of stimulation patterns presented to the body surface, providing a means to parametrically relate neural representation and subjective percept, and (b) applies this method to demonstrate the existence of 'somatotopic maps' of hot and painful stimulus patterns independent from mechanoceptive co-activation. Brief (90 ms) CO2 laser pulses were presented in an array of multiple stimulation sites on the dorsal forearms (N. radialis area, C7 dermatome) of healthy subjects. Perceived locations were indicated with a 3D tracker without touching the skin, and (mis-)localizations in distal-proximal direction were analyzed. Stimuli were localized with overall mean errors of 22 mm (SD: 16 mm) toward the wrist and 24 mm (SD: 18 mm) toward the elbow. Somatotopic representation of thermal-nociceptive stimuli could be demonstrated in all subjects, independent from mechanoceptive co-activation. The perceptual maps revealed striking individual (mis-)localization patterns, many subjects exhibiting 'stretched', some 'condensed' somatotopic representations. In estimating the mapping parameters from physical to perceptual space linear regressions generally provided a good fit (adj. R2>0.80 in 10 out of 12 subjects). Nonlinear models were advantageous in some subjects only. Our method can be useful in assessing inter-individual differences or experimentally induced shifts in somatotopic processing.