Granulomatous myocarditis arising from intravesical Bacillus Calmette-Guérin therapy leading to death diagnosed by postmortem examination: a case report.

BACKGROUND: Intravesical Bacillus Calmette-Guérin (BCG) is used as a standard adjuvant therapy for non-muscle invasive urothelial cancer. Most patients tolerate the treatment well, with mild side effects. Systemic complications are extremely rare, occur due to BCG dissemination and are associated with immunocompromised state and urothelial breach. CASE PRESENTATION: We present a case of a 78-year-old male, a former smoker, with history of non-muscle invasive urothelial carcinoma status post partial resection followed by intravesical BCG therapy. An autopsy was performed due to the sudden nature of his death. Autopsy showed multiple necrotizing granulomas in the brain, atrium, ventricles, lungs, kidneys, and urinary bladder. Stains for acid-fast bacilli and fungi were negative. In addition, bilateral lungs showed evidence of bronchopneumonia secondary to cytomegalovirus. CONCLUSION: Granulomatous myocarditis arising from BCG therapy is extremely rare. Our patient with urothelial cancer treated with BCG developed multiorgan granulomas, most likely due to a hypersensitivity reaction to intravesical BCG. Arrhythmia induced by granulomatous myocarditis was the cause of his death. Although there have been few cases of systemic BCG-osis causing fatal sepsis leading to death, a cardiac cause of death is unique.

A Rare Case of Intraosseous Papillary Hemangioma of the Head and Neck.

Papillary hemangioma is a novel variant of intravascular hemangioma. It is more common in adults and has a male predominance. Most tumors reported so far are solitary and cutaneous. Here we present a rare case of an intraosseous papillary hemangioma involving the frontal bone. Brain imaging in a 69-year-old man with a slowly enlarging swelling on the right frontal area following an accidental fall demonstrated a 4.5 cm × 1.7 cm × 4.2 cm mass originating from the right frontal bone, with a tiny defect on the orbital roof. A malignant process was favored, and the mass was removed. Histopathology revealed a vascular lesion showing intraosseous distribution with foci of extension into the fibrous connective tissue. There were areas of plump endothelial cells with intracytoplasmic hyaline globules arranged in papillary configuration. The lesional cells were immunoreactive with CD34. AE1/AE3, EMA, PR, D2-40, inhibin, and S100 stains were negative. Ki-67 was low. This is the first intraosseous and second noncutaneous papillary hemangioma. Clinically it differs from other cases by the presence of trauma as a preceding event. Since its prognosis is unknown such patients should be monitored for recurrence or malignant transformation.

Evaluation of ChatGPT pathology knowledge using board-style questions.

OBJECTIVES: ChatGPT is an artificial intelligence chatbot developed by OpenAI. Its extensive knowledge and unique interactive capabilities enable its use in various innovative ways in the medical field, such as writing clinical notes and simplifying radiology reports. Through this study, we aimed to analyze the pathology knowledge of ChatGPT to advocate its role in transforming pathology education. METHODS: The American Society for Clinical Pathology Resident Question Bank 2022 was used to test ChatGPT, version 4. Practice tests were created in each subcategory and answered based on the input that ChatGPT provided. Questions that required interpretation of images were excluded. We analyzed ChatGPT performance and compared it with average peer performance. RESULTS: The overall performance of ChatGPT was 56.98%, lower than that of the average peer performance of 62.81%. ChatGPT performed better on clinical pathology (60.42%) than on anatomic pathology (54.94%). Furthermore, its performance was better on easy questions (68.47%) than on intermediate (52.88%) and difficult questions (37.21%). CONCLUSIONS: ChatGPT has the potential to be a valuable resource in pathology education if trained on a larger, specialized medical data set. Those relying on it (in its current form) solely for the purpose of pathology training should be cautious.

A Bystander Effect of Lung Cancer Chemotherapy on Chronic Echinococcal Disease.

Hydatid cystic disease is a parasitic infestation caused by Echinococcus granulosus and commonly manifests as hepatic and pulmonary cysts. When feasible, based on cyst size and location, surgical resection is potentially curative. Post-surgical recurrence of disease is encountered in up to 25% of patients. Secondary peritoneal contamination is a recognized complication in 5-10% of cases. Disseminated disease is usually palliated using systemic anti-parasitic agents such as benzimidazoles, albendazole and mebendazole but worsening of disease post-systemic treatment is frequent in 14-25% of patients. In this report, we share our experience of a patient with long-standing, chronic disseminated hydatidosis and subsequent diagnosis of non-small cell lung cancer who manifested evidence of reduced activity of the echinococcal disease following institution of chemotherapy for his new diagnosis of lung cancer. There was significant reduction in the serum level of anti-echinococcal antibody titers in tandem with chemotherapy administration. There was also minimal but notable decrease in the size of the cysts on serial cross-sectional imaging obtained for monitoring cancer response to chemotherapy. This intriguing observation of a possible benefit of anticancer chemotherapy against echinococcal disease in this index case may provide new insights for therapeutic exploration in disseminated echinococcal disease.

Striatum-based circuitry of adolescent depression and anhedonia.

OBJECTIVE: Striatum-based circuits have been implicated in both major depressive disorder (MDD) and anhedonia, a symptom that reflects deficits of reward processing. Yet adolescents with MDD often exhibit a wide range of anhedonia severity. Addressing this clinical phenomenon, we aimed to use intrinsic functional connectivity (iFC) to study striatum-based circuitry in relation to categorical diagnosis of MDD and anhedonia severity. METHOD: A total of 21 psychotropic medication-free adolescents with MDD and 21 healthy controls (HC), group-matched for age and sex, underwent resting-state functional magnetic resonance imagining (fMRI) scans. Voxelwise maps indicating correlation strengths of spontaneous blood-oxygenation-level-dependent (BOLD) signals among 6 bilateral striatal seeds (dorsal caudate, ventral caudate, nucleus accumbens, dorsal-rostral putamen, dorsal-caudal putamen, ventral-rostral putamen) and the remaining brain regions were compared between groups. Relationships between striatal iFC and severity of MDD and anhedonia were examined in the MDD group. Analyses were corrected for multiple comparisons. RESULTS: Adolescents with MDD manifested increased iFC between all striatal regions bilaterally and the dorsomedial prefrontal cortex (dmPFC), as well as between the right ventral caudate and the anterior cingulate cortex (ACC). MDD severity was associated with iFC between the striatum and midline structures including the precuneus, posterior cingulate cortex, and dmPFC. However, distinct striatal iFC patterns involving the pregenual ACC, subgenual ACC, supplementary motor area, and supramarginal gyrus were associated with anhedonia severity. CONCLUSIONS: Although MDD diagnosis and severity were related to striatal networks involving midline cortical structures, distinct circuits within the reward system were associated with anhedonia. Findings support the incorporation of both categorical and dimensional approaches in neuropsychiatric research.

The beta subunit of voltage-gated Ca2+ channels interacts with and regulates the activity of a novel isoform of Pax6.

Ca(2+) channel beta subunits (Ca(v)betas) are essential for regulating the surface expression and gating of high voltage-activated Ca(2+) channels through their interaction with Ca(2+) channel alpha(1) subunits. In efforts to uncover new interacting partners and new functions for Ca(v)beta, we identified a new splicing isoform of Pax6, a transcription factor crucial for the development of the eye, nose, brain, and pancreas. Pax6 contains two DNA binding domains (paired domain and homeodomain), a glycine-rich linker connecting these two domains and a C-terminal proline-, serine-, and threonine-rich transactivation domain. The protein sequence and function of Pax6 are highly conserved from invertebrate to human. The newly isolated isoform, named Pax6(S), retains the paired domain, linker, and homeodomain of Pax6, but its C terminus is composed of a truncated classic proline, serine, and threonine domain and a unique S tail. Pax6(S) shows a similar level of transcriptional activity in vitro as does Pax6, but only in primates is the protein sequence highly conserved. Its spatial-temporal expression profiles are also different from those of Pax6. These divergences suggest a noncanonical role of Pax6(S) during development. The interaction between Pax6(S) and Ca(v)beta is mainly endowed by the S tail. Co-expression of Pax6(S) with a Ca(2+) channel complex containing the beta(3) subunit in Xenopus oocytes does not affect channel properties. Conversely, however, beta(3) is able to suppress the transcriptional activity of Pax6(S). Furthermore, in the presence of Pax6(S), beta(3) is translocated from the cytoplasm to the nucleus. These results suggest that full-length Ca(v)beta may act directly as a transcription regulator independent of its role in regulating Ca(2+) channel activity.

Origin of the voltage dependence of G-protein regulation of P/Q-type Ca2+ channels.

G-protein (Gbetagamma)-mediated voltage-dependent inhibition of N- and P/Q-type Ca(2+) channels contributes to presynaptic inhibition and short-term synaptic plasticity. The voltage dependence derives from the dissociation of Gbetagamma from the inhibited channels, but the underlying molecular and biophysical mechanisms remain largely unclear. In this study we investigated the role in this process of Ca(2+) channel beta subunit (Ca(v)beta) and a rigid alpha-helical structure between the alpha-interacting domain (AID), the primary Ca(v)beta docking site on the channel alpha(1) subunit, and the pore-lining IS6 segment. Gbetagamma inhibition of P/Q-type channels was reconstituted in giant inside-out membrane patches from Xenopus oocytes. Large populations of channels devoid of Ca(v)beta were produced by washing out a mutant Ca(v)beta with a reduced affinity for the AID. These beta-less channels were still inhibited by Gbetagamma, but without any voltage dependence, indicating that Ca(v)beta is indispensable for voltage-dependent Gbetagamma inhibition. A truncated Ca(v)beta containing only the AID-binding guanylate kinase (GK) domain could fully confer voltage dependence to Gbetagamma inhibition. Gbetagamma did not alter inactivation properties, and channels recovered from Gbetagamma inhibition exhibited the same activation property as un-inhibited channels, indicating that Gbetagamma does not dislodge Ca(v)beta from the inhibited channel. Furthermore, voltage-dependent Gbetagamma inhibition was abolished when the rigid alpha-helix between the AID and IS6 was disrupted by insertion of multiple glycines, which also eliminated Ca(v)beta regulation of channel gating, revealing a pivotal role of this rigid alpha-helix in both processes. These results suggest that depolarization-triggered movement of IS6, coupled to the subsequent conformational change of the Gbetagamma-binding pocket through a rigid alpha-helix induced partly by the Ca(v)beta GK domain, causes the dissociation of Gbetagamma and is fundamental to voltage-dependent Gbetagamma inhibition.

Effect of exercise on lung function tests in hay fever.

The patients in this study were divided into three groups on the basis of V50. Group I included completely normal subjects with normal V50 before and after exercise. Group II showed a normal initial V50 which decreased following exercise. This indicates small airways dysfunction which is exaggerated by exercise. Group II showed abnormal V50 initially which remained unchanged after exercise, suggesting more permanent impairment of the small airways function. Thus significant physiologic abnormalities were identified in patients belonging to Group II and Group III.

Transduction of isoniazid susceptibility-resistance and streptomycin resistance in mycobacteria.

Transduction of resistance to isoniazid and streptomycin as well as susceptibility to isoniazid in Mycobacterium smegmatis SN2 has been demonstrated. A method has been described for the selection of isoniazid-susceptible variants after transduction of susceptibility.