Hypercalcemia is an uncommon but clinically significant complication of pediatric malignancies that often presents with symptoms. However, in this case series, we report 4 children with nonspecific symptoms of hypercalcemia detected incidentally on routine biochemical evaluation at the time of leukemia diagnosis.

Patients, 5 to 9 years of age, had underlying malignancies, including Hodgkin lymphoma (stage IIA), pre-B-cell acute lymphoblastic leukemia, and acute promyelocytic leukemia. All the patients presented with severe hypercalcemia, necessitating prompt intervention. Treatment consisted of hyperhydration, loop diuretics, bisphosphonates, and calcitonin, along with the management of the underlying malignancy. Successful resolution of hypercalcemia was achieved in all cases, with no future recurrence.

This case series highlights the importance of the routine biochemical screening for newly diagnosed pediatric malignancies, particularly for nonspecific symptoms of hypercalcemia, which may otherwise go unrecognized. Although hypercalcemia in hematological malignancies is well-documented, our findings stress the silent presentation and reinforce the clinical need for early identification to avoid metabolic complications.

Cancer brings about an enormous threat to human health,making the exploration of its mechanisms and therapeutic strategies a current focal point and challenge in research.Bacteriophages are integral components of the human microbiome,and studies have shown their influences on tumor growth and metastasis and their pivotal role in cancer treatment.This article elucidates the mechanisms by which bacteriophages impact the occurrence and development of cancer from their interactions with cancer cells,effects on bacteria,and influence on the immune system.Additionally,it explores bacteriophage-based strategies in cancer treatment and their potential in this field.This article aims to bring new thoughts and insights to the research in this field.

A 10-year-old mixed-breed dog was presented with progressive neurological deficits suggestive of polyneuropathy. CT and MRI revealed no relevant abnormalities, whereas the CSF analysis showed a marked lymphocytic pleocytosis, immunocytochemically classified as T-cell lymphoma. Chemotherapy ensued with no improvement of clinical signs. Cerebrospinal fluid reanalysis still revealed a mild lymphocytic pleocytosis. MRI of the brain and spinal cord solely showed a reduced ventral subarachnoid and epidural space (Th11-L2) and mild enlargement of the central canal in this area. Postmortem examination revealed thickening of the spinal nerve roots and ganglia. Histologically, a marked intraspinal-subdural and intraneural, as well as intra-ganglionic, infiltration by large lymphocytes in the peripheral nervous system was visible. Immunohistochemically, the infiltrating lymphoblasts were CD3 positive, confirming T-cell origin. Neurolymphomatosis is a rarely described neoplastic disease in dogs. The present case highlights the importance of analysis of CSF in neurologically abnormal dogs.

Patients with inflammatory bowel disease (IBD) often consider their gastroenterologist to be the primary provider of care. To improve the care delivered to patients with IBD, health maintenance issues need to be addressed by the gastroenterology team. In particular, documentation and recommendation for vaccinations are crucial because more than 70% of patients with IBD will at some time be on immune-modifying therapies that may increase the risk for infections, many of which are preventable with vaccinations. Health maintenance recommendations addressed in this guideline include the safety and appropriate timing of vaccinations, screening for osteoporosis, cervical cancer, melanoma and non-melanoma skin cancer and screening for depression, anxiety, and need for smoking cessation. To accomplish these health maintenance goals, coordination among the primary care provider, gastroenterology team, and other specialists is necessary.

Retinoblastoma, a potentially fatal pediatric intraocular malignancy, is now curable with intravenous and intra-arterial (IAC) chemotherapy. In this report, the authors describe globe volume asymmetry, a lesser-known sequela of IAC, as well as the hemodynamics of a tumor-laden eye, pattern of eyeball growth following IAC, and potential mechanisms of amblyopia in retinoblastoma survivors. [J Pediatr Ophthalmol Strabismus. 2025;62(4):e46-e50.].

Anti-apoptotic B-cell lymphoma-2 (BCL-2) family proteins are frequently overexpressed in various cancers, playing a pivotal role in cancer initiation and progression, as well as intrinsic or acquired resistance to therapy. Although inhibitors targeting BCL-2, such as Venetoclax, have shown efficacy in hematological malignancies, their therapeutic potential in solid tumors remains limited. Identifying novel molecular targets to overcome resistance to these inhibitors is of significant clinical importance. Here, we provide evidence of a strong synthetic lethality between WSB2, a previously underexplored substrate-binding receptor of the Cullin 5-RBX2-Elongin B/C (CRL5) E3 ubiquitin ligase complex, and anti-apoptotic BCL-2 family proteins. Mechanistically, WSB assembles a CRL5 E3 ubiquitin ligase complex that facilitates the ubiquitination and subsequent proteasomal degradation of NOXA, a pro-apoptotic BCL-2 family protein. Loss of WSB2 leads to a substantial accumulation of NOXA in both cultured cell lines and knockout mouse tissues. While WSB2 deficiency alone does not significantly impact spontaneous apoptosis, it sensitizes cells to apoptosis when anti-apoptotic BCL-2 family proteins are either genetically depleted or pharmacologically inhibited. Moreover, WSB2 is overexpressed in several human cancer types. These findings identify WSB2 as a critical regulator of mitochondrial apoptosis and reveal the dysregulation of the WSB2-NOXA axis as a key factor contributing to apoptosis resistance in cancer cells. Targeting both WSB2 and anti-apoptotic BCL-2 family proteins holds promising therapeutic potential for overcoming resistance in human cancers.

Drug discovery balances many factors as it identifies compounds for clinical testing, including compound efficacy, safety, pharmacokinetic (PK) properties, commercial feasibility, competitive positioning, and organizational pressures to move quickly with limited knowledge. When considering target engagement within clinically acceptable dosing constraints, design elements often balance potency requirements against the required extent of target engagement, which subsequently inform the PK design criteria (e.g. absorption and half-life considerations). Hence, an early understanding of the magnitude and duration of target engagement can focus design teams by providing well defined design criteria. To this end, an in vitro target engagement assay has been developed to bin targets and compounds by the type of target engagement profile required for efficacy (cellular anti-proliferation). This in turn directionally informs on the required concentration profile most aligned with the efficacy readout, bucketing results into three primary categories that drive efficacy: high transient concentrations, average concentrations, and threshold concentrations. This manuscript will outline the methodology developed for this early target coverage assessment and provide examples with selected compounds spanning molecularly targeted and cytotoxic oncology small molecules.

The predictive value of preoperative testosterone levels for erectile function (ED) preservation after nerve-sparing radical prostatectomy (NSRP) remains controversial, with conflicting evidence regarding its clinical utility for surgical planning and patient counseling.

Comprehensive searches of MEDLINE, Cochrane Library, and Embase were conducted through May 1, 2025. Observational studies reporting adjusted odds ratios (ORs) with 95% confidence intervals (CIs) for postoperative ED stratified by preoperative testosterone levels were included. Random-effects models were used for meta-analysis, with subgroup analyses by study design and surgical approach. Outcomes included postoperative erectile function status assessed via validated questionnaires or clinical evaluations at ≥ 6-month follow-up.

Four cohort studies involving 2,312 patients were included in the meta-analysis. Pooled analysis demonstrated significantly increased ED risk with lower preoperative testosterone levels (OR = 1.72, 95%CI: 1.26-2.35; P = 0.001; I² = 74.2%). Consistent associations emerged across subgroups: retrospective studies (OR = 2.20, 1.25-3.87), prospective studies (OR = 1.33, 1.29-1.38), laparoscopic procedures (OR = 1.55, 1.17-2.06), and robot-assisted approaches (OR = 3.02, 1.41-6.46).

Current evidence demonstrates that low preoperative serum testosterone levels significantly increase the risk of ED following NSRP. Furthermore, preoperative testosterone assessment enables urologists to implement standardized postoperative management protocols, including targeted rehabilitation strategies and optimized follow-up schedules for high-risk patients.

Fever of unknown origin is one of the most challenging clinical symptoms, with complex etiologies including infections, malignancies, and rheumatic immune diseases. Lymphoma is a common malignant tumor associated with fever of unknown origin, and its early diagnosis is often difficult because routine laboratory tests and imaging manifestations may fail to provide a definitive diagnosis. Here, we report the case of a patient with natural killer/T-cell lymphoma who primarily presented with long-term fever and pharyngodynia. The patient sought medical care at several hospitals and underwent multiple laryngoscopies and a biopsy of the tongue base. After >3 months from the time of initial presentation, the diagnosis was ultimately confirmed through the second biopsy of the tongue base. The case highlights the diagnostic challenges of lymphoma with atypical symptoms in the context of fever of unknown origin and underscores the role of infectious disease physicians in diagnosing noninfectious diseases related to fever of unknown origin.

Glottis cancer, a prevalent subtype of laryngeal malignancies, is frequently encountered in clinical practice in LMIC (Lower Middle Income Countries). This case report presents an extraordinary occurrence of T1 glottis cancer, shedding light on a rare clinical scenario. Typically, early-stage glottis cancers, including T1 tumours, exhibit a remarkable rarity of occult lymph node involvement, with estimates indicating a prevalence of less than five percent. However, in this significant case, seen at the Cyberknife and Tomotherapy Centre, Jinnah Postgraduate Medical Centre (JPMC), Karachi, in 2022, the patient faced a recurrence of the disease, manifesting within the sternocleidomastoid muscle-a highly unusual presentation. Notably, this recurrence occurred without any discernible involvement of cervical nodes or primary site, i.e. larynx.