BACKGROUND: Colorectal signet-ring cell carcinoma (CSRCC) is a rare clinical entity which accounts for approximately 1% of all colorectal cancers. Although multiple studies concerning this specific topic have been published in the past decades, the pathogenesis, associated risk factors, and potential implications on treatment are still poorly understood. Besides the low incidence, historically confusing histological criteria have resulted in confusing data. Nevertheless, the rising incidence of CSRCC along with relatively young age at presentation and associated dismal prognosis, highlight the actual interest to synthesize the known literature regarding CSRCC.
OBJECTIVE: To provide an updated overview of risk factors, prognosis, and management of CSRCC.
METHODS: A literature search in the MEDLINE/PubMed database was conducted with the following search terms used: \'Signet ring cell carcinoma\' and \'colorectal\'. Studies in English language, published after January 1980, were included. Studies included in the qualitative synthesis were evaluated for content concerning epidemiology, risk factors, and clinical, diagnostic, histological, and molecular features, as well as metastatic pattern and therapeutic management. If possible, presented data was extracted in order to present a more detailed overview of the literature.
RESULTS: In total, 67 articles were included for qualitative analysis, of which 54 were eligible for detailed data extraction. CSRCC has a reported incidence between 0.1%-2.4% and frequently presents with advanced disease stage at the time of diagnosis. CSRCC is associated with an impaired overall survival (5-year OS: 0%-46%) and a worse stage-corrected outcome compared to mucinous and not otherwise specified adenocarcinoma. The systematic use of exploratory laparoscopy to determine the presence of peritoneal metastases has been advised. Surgery is the mainstay of treatment, although the rates of curative resection in CSRCC (21%-82%) are lower compared to those in other histological types. In case of peritoneal metastasis, cytoreductive surgery with hyperthermic intraperitoneal chemotherapy should only be proposed in selected patients.
CONCLUSIONS: CSRCC is a rare clinical entity most often characterized by young age and advanced disease at presentation. As such, diagnostic modalities and therapeutic approach should be tailored accordingly.

Duchenne Muscular Dystrophy (DMD) is an X-linked recessive genetic disorder characterized by progressive and severe muscle weakening and degeneration. Among the various forms of muscular dystrophy, it stands out as one of the most common and impactful, predominantly affecting boys. The condition arises due to mutations in the dystrophin gene, a key player in maintaining the structure and function of muscle fibers. The manuscript explores the structural features of dystrophin protein and their pivotal roles in DMD. We present an in-depth analysis of promising therapeutic approaches targeting dystrophin and their implications for the therapeutic management of DMD. Several therapies aiming to restore dystrophin protein or address secondary pathology have obtained regulatory approval, and many others are ongoing clinical development. Notably, recent advancements in genetic approaches have demonstrated the potential to restore partially functional dystrophin forms. The review also provides a comprehensive overview of the status of clinical trials for major therapeutic genetic approaches for DMD. In addition, we have summarized the ongoing therapeutic approaches and advanced mechanisms of action for dystrophin restoration and the challenges associated with DMD therapeutics.

The clinical spectrum of primary Sjögren\'s syndrome (PSS) extends beyond its classical manifestations. This work explores an unusual aspect of PSS, namely the initial presentation of cranial neuropathy. The study was conducted over a period of 22 months, from January 2022 to October 2023. Of 58 PSS patients, only five (four women and one man) had cranial neuropathy as their initial manifestation. Only one patient had sixth cranial nerve involvement, three had acute optic neuritis (second cranial nerve), and three had fifth cranial nerve involvement. The diagnosis of PSS was retained according to the 2016 ACR-EULAR criteria. All patients received symptomatic and immunosuppressive treatments. The course was favorable for all patients. The purpose of this case series is to show that cranial neuropathy can be the initial manifestation of PSS, which should be systematically investigated after the elimination of the most common etiologies of cranial neuropathy, particularly in the elderly.

Claudin-18.2 (CLDN18.2) is a member of the tight junction protein family and is a highly selective biomarker with frequent abnormal expression during the occurrence and development of various primary malignant tumors, including gastric cancer (GC) and esophago-gastric junction adenocarcinomas (EGJA). For these reasons, CLDN18.2 has been investigated as a therapeutic target for GC/EGJA malignancies. Recently, zolbetuximab has been proposed as a new standard of care for patients with CLDN18.2-positive, HER2-negative, locally advanced and metastatic GC/EGJA. The use of CLDN18 IHC assays to select patients who might benefit from anti-CLDN18.2 therapy is currently entering clinical practice. In this setting, pathologists play a central role in therapeutic decision-making. Accurate biomarker assessment is essential to ensure the best therapeutic option for patients. In the present review, we provide a comprehensive overview of available evidence on CLDN18.2 testing and its impact on the therapeutic management of patients with GC/EGJA, as well as some practical suggestions for CLDN18.2 staining interpretation and potential pitfalls in the real-world setting.

The dual burden of pulmonary tuberculosis (PTB) and diabetes mellitus (DM) is a major global public health concern. There is increasing evidence to indicate an association between PTB and DM. DM is associated with immune dysfunction and altered immune components. Hyperglycemia weakens the innate immune response by affecting the function of macrophages, dendritic cells, neutrophils, and natural killer cells, and also disrupts the adaptive immune response, thus promoting the susceptibility of PTB in patients with DM. Antituberculosis drugs often cause the impairment of liver and kidney function in patients with PTB, and the infection with Mycobacterium tuberculosis weaken pancreatic endocrine function by causing islet cell amyloidosis, which disrupts glucose metabolism and thus increases the risk of developing DM in patients with PTB. The present review discusses the association between PTB and DM from the perspective of epidemiology, pathogenesis, and treatment management. The present review aims to provide information for the rational formulation of treatment strategies for patients with PTB-DM.

UNASSIGNED: Proximal phalangeal fractures are common and can have a significant impact on hand function. Therefore, it is important to optimise post-operative rehabilitation. A scoping review was undertaken to map the existing evidence on rehabilitation of proximal phalangeal fractures of the fingers in adults.
UNASSIGNED: A comprehensive search was conducted which included database searching, reference searching, hand searching of journals, and searching for grey literature. Eight articles were included after screening for eligibility.
UNASSIGNED: Three studies researched surgical interventions and five studies conservative management. The immobilisation period varied between 5 days to 3 weeks in the surgical studies, and between 3 to 7 weeks in the conservative studies. Active exercise therapy was started immediately with conservative management, while in the surgical studies time to commence exercises varied between 5 days and 3 weeks. All studies reported good results in mobility with a mean total active motion ranging from 240° to 258.9°. Patients reported little pain at final follow-up and grip strength recovered to 96% compared to the unaffected side. Studies reporting on function and patient satisfaction lacked transparency.
UNASSIGNED: All studies had a moderate to high risk of bias and the results of the included studies should therefore be interpreted with caution. More high-quality randomised controlled studies with an a priori research protocol and a standard set of outcome measures are necessary to research whether early motion, an intrinsic plus splint leaving the wrist free, and the inclusion of additional treatment modalities can result in a better and/or faster recovery.

Catecholaminergic polymorphic ventricular tachycardia (CPVT) is an inherited arrhythmia syndrome characterized by bidirectional or polymorphic ventricular arrhythmia provoked by exercise or emotion. Most cases are caused by pathogenic variants in the gene encoding the cardiac ryanodine receptor (RYR2). The options for treating patients with CPVT have increased during the years, and evidence suggests that these have led to lower arrhythmic event rates. In addition, numerous potential new therapies are being investigated. In this review, we summarize the state of knowledge on both established and potential future treatment strategies for patients with CPVT and describe our approach to their management.

The objective was to evaluate the comparative effectiveness and safety of pharmacological and nonpharmacological management options for atrial fibrillation/atrial flutter with rapid ventricular response (AFRVR) in patients with acute decompensated heart failure (ADHF) in the acute care setting.
This study was a systematic review of observational studies or randomized clinical trials (RCT) of adult patients with AFRVR and concomitant ADHF in the emergency department (ED), intensive care unit, or step-down unit. The primary effectiveness outcome was successful rate or rhythm control. Safety outcomes were adverse events, such as symptomatic hypotension and venous thromboembolism.
A total of 6577 unique articles were identified. Five studies met inclusion criteria: one RCT in the inpatient setting and four retrospective studies, two in the ED and the other three in the inpatient setting. In the RCT of diltiazem versus placebo, 22 patients (100%) in the treatment group had a therapeutic response compared to 0/15 (0%) in the placebo group, with no significant safety differences between the two groups. For three of the observational studies, data were limited. One observation study showed no difference between metoprolol and diltiazem for successful rate control, but worsening heart failure symptoms occurred more frequently in those receiving diltiazem compared to metoprolol (19 patients [33%] vs. 10 patients [15%], p = 0.019). A single study included electrical cardioversion (one patient exposed with failure to convert to sinus rhythm) as nonpharmacological management. The overall risk of bias for included studies ranged from serious to critical. Missing data and heterogeneity of definitions for effectiveness and safety outcomes precluded the combination of results for quantitative meta-analysis.
High-level evidence to inform clinical decision making regarding effective and safe management of AFRVR in patients with ADHF in the acute care setting is lacking.

While the incidence of gastric cancer (GC) in general has decreased worldwide in recent decades, the incidence of diffuse cancer historically comprising poorly cohesive cells-GC (PCC-GC) and including signet ring cell cancer is rising. Literature concerning PCC-GC is scarce and unclear, mostly due to a large variety of historically used definitions and classifications. Compared to other histological subtypes of GC, PCC-GC is nevertheless characterized by a distinct set of epidemiological, histological and clinical features which require a specific diagnostic and therapeutic approach. The aim of this review was to provide an update on the definition, classification and therapeutic strategies of PCC-GC. We focus on the updated histological definition of PCC-GC, along with its implications on future treatment strategies and study design. Also, specific considerations in the diagnostic management are discussed. Finally, the impact of some recent developments in the therapeutic management of GC in general such as the recently validated taxane-based regimens (5-Fluorouracil, leucovorin, oxaliplatin and docetaxel), the use of hyperthermic intraperitoneal chemotherapy as well as pressurized intraperitoneal aerosol chemotherapy and targeted therapy have been reviewed in depth for their relative importance for PCC-GC in particular.

The potential relationship between diabetes and COVID-19 has been evaluated. However, new knowledge is rapidly emerging. In this study, we systematically reviewed the relationship between viral cell surface receptors (ACE2, AXL, CD147, DC-SIGN, L-SIGN and DPP4) and SARS-CoV-2 infection risk, and emphasized the implications of ACE2 on SARS-CoV-2 infection and COVID-19 pathogenesis. Besides, we updated on the two-way interactions between diabetes and COVID-19, as well as the treatment options for COVID-19 comorbid patients from the perspective of ACE2. The efficacies of various clinical chemotherapeutic options, including anti-diabetic drugs, renin-angiotensin-aldosterone system inhibitors, lipid-lowering drugs, anticoagulants, and glucocorticoids for COVID-19 positive diabetic patients were discussed. Moreover, we reviewed the significance of two different forms of ACE2 (mACE2 and sACE2) and gender on COVID-19 susceptibility and severity. This review summarizes COVID-19 pathophysiology and the best strategies for clinical management of diabetes patients with COVID-19.