Internal medicine in the 21st century: Back to the future.

Healthcare systems face multiple challenges arising from demographic factors (population aging) and epidemiological factors (rise of chronic diseases and patients with multimorbidity) as well as threats to their financial sustainability when maintaining equitable access to medical and technological advances. Current healthcare models, based on specialized medical care, lead to fragmented care that can be harmful to the patient and is inefficient for the system due to the overuse of redundant, low-value medical acts. Internal medicine is the hospital-centered general medical specialty par excellence, providing a comprehensive and holistic vision that is centered on the patient and not on the disease. Internists should be the leading physicians in the hospital setting for complex patients with or those with an uncertain diagnosis. Internists must play a key role, as hospitalists do, in the continued care of acute patients hospitalized for medical or surgical diseases, establishing shared care models in multidisciplinary teams. Likewise, to guarantee continuity of care for chronic patients, internists must establish mechanisms for collaboration with primary care and nursing, participating in the development of new out-of-hospital care models that use the available technological resources. Internal medicine should play a leading role in graduate and postgraduate medical education to promote a holistic vision among medical students and residents in medical subspecialties.

Indoor air pollution impacts cardiovascular autonomic control during sleep and the inflammatory profile.

The present study explores the modifications of cardiovascular autonomic control (CAC) during wake and sleep time and the systemic inflammatory profile associated with exposure to indoor air pollution (IAP) in a cohort of healthy subjects. Twenty healthy volunteers were enrolled. Indoor levels of fine particulate matter (PM2.5), nitrogen dioxide (NO2) and volatile organic compounds (VOCs) were monitored using a portable detector for 7 days. Together, a 7-day monitoring was performed through a wireless patch that continuously recorded electrocardiogram, respiratory activity and actigraphy. Indexes of CAC during wake and sleep time were derived from the biosignals: heart rate and low-frequency to high-frequency ratio (LF/HF) index of sympathovagal balance with higher values corresponding to a predominance of the sympathetic branch. Cyclic variation of heart rate index (CVHRI events/hour) during sleep, a proxy for the evaluation of sleep apnea, was assessed for each night. After the monitoring, blood samples were collected to assess the inflammatory profile. Regression and correlation analysis were performed. A positive association between VOC exposure and the CVHRI (Δ%=+0.2% for 1µg/m3 VOCs, p=0.008) was found. The CVHRI was also positively associated with LF/HF during sleep, thus higher CVHRI values corresponded to a shift of the sympathovagal balance towards a sympathetic predominance (r=0.52; p=0.018). NO2 exposure was positively associated with both the pro-inflammatory biomarker TREM-1 and the anti-inflammatory biomarker IL-10 (Δ%=+1.2% and Δ%=+2.4%, for 1µg/m3 NO2; p=0.005 and p=0.022, respectively). The study highlights a possible causal relationship between IAP exposure and higher risk of sleep apnea events, associated with impaired CAC during sleep, and a pro-inflammatory state counterbalanced by an increased anti-inflammatory response in healthy subjects. This process may be disrupted in vulnerable populations, leading to a harmful chronic pro-inflammatory profile. Thus, IAP may emerge as a critical and often neglected risk factor for the public health that can be addressed through targeted preventive interventions.

Long-Term Outcome in Adult Patients with Drug-Resistant Epilepsy Submitted to Vagus Nerve Stimulation.

Epilepsy treatment primarily involves antiseizure medications (ASMs) to eliminate seizures and improve the quality of life, but many patients develop drug-resistant epilepsy (DRE), necessitating alternative interventions. This study aimed to evaluate the long-term efficacy and safety of vagus nerve stimulation (VNS) in managing DRE. We retrospectively analyzed data from 105 adult patients treated at Agostino Gemelli Hospital from 1994 to 2022. Among the 73 patients with follow-up data, 80.8% were responders, experiencing significant reductions in seizure frequency over an average follow-up period of 9.4 years. Although 19.2% were non-responders, many of these patients still opted for generator replacements due to improvements in quality of life, such as fewer falls and shorter post-ictal periods. The overall complication rate was 12.3%, with most complications being mild and manageable. These findings suggest that VNS offers substantial long-term benefits for patients with DRE, improving seizure control and quality of life. This study underscores the importance of VNS as a viable long-term treatment option for DRE, highlighting its potential to significantly enhance patient outcomes and quality of life.

Soluble Triggering Receptors Expressed on Myeloid Cells (sTREM) in Acute Ischemic Stroke: A Potential Pathway of sTREM-1 and sTREM-2 Associated with Disease Severity.

In 2022, stroke emerged as the most significant cerebrovascular disorder globally, causing 6.55 million deaths. Microglia, crucial for CNS preservation, can exacerbate brain damage in ischemic stroke by triggering neuroinflammation. This process is mediated by receptors on microglia, triggering receptors expressed on myeloid cells (TREM-1 and TREM-2), which have contrasting roles in neuroinflammation. In this study, we recruited 38 patients within 4.5 h from the onset of ischemic stroke. The degree of severity was evaluated by means of the National Institutes of Health Stroke Scale (NIHSS) at admission (T0) and after one week of ischemic events (TW) and the Modified Rankin Scale (mRS) at three months. The plasma concentration of TREMs (sTREM) was analyzed by next-generation ELISA at T0 and TW. The sTREM-1 concentrations at T0 were associated with mRS, while the sTREM-2 concentrations at T0 were associated with both the NIHSS at T0 and the mRS. A strong correlation between sTREM-1 and sTREM-2 was observed, suggesting a dependent modulation of the levels. This study provides insights into the potential pathway of TREM-1 and TREM-2 as a future biomarker for stratifying high-risk patients with ischemic stroke.

Intraoperative microelectrode recording during asleep deep brain stimulation of subthalamic nucleus for Parkinson Disease. A case series with systematic review of the literature.

The use of microelectrode recording (MER) during deep brain stimulation (DBS) for Parkinson Disease is controversial. Furthermore, in asleep DBS anesthesia can impair the ability to record single-cell electric activity.The purpose of this study was to describe our surgical and anesthesiologic protocol for MER assessment during asleep subthalamic nucleus (STN) DBS and to put our findings in the context of a systematic review of the literature. Sixty-three STN electrodes were implanted in 32 patients under general anesthesia. A frameless technique using O-Arm scanning was adopted in all cases. Total intravenous anesthesia, monitored with bispectral index, was administered using a target controlled infusion of both propofol and remifentanil. A systematic review of the literature with metanalysis on MER in asleep vs awake STN DBS for Parkinson Disease was performed. In our series, MER could be reliably recorded in all cases, impacting profoundly on electrode positioning: the final position was located within 2 mm from the planned target only in 42.9% cases. Depth modification > 2 mm was necessary in 21 cases (33.3%), while in 15 cases (23.8%) a different track was used. At 1-year follow-up we observed a significant reduction in LEDD, UPDRS Part III score off-medications, and UPDRS Part III score on medications, as compared to baseline. The systematic review of the literature yielded 23 papers; adding the cases here reported, overall 1258 asleep DBS cases using MER are described. This technique was safe and effective: metanalysis showed similar, if not better, outcome of asleep vs awake patients operated using MER. MER are a useful and reliable tool during asleep STN DBS, leading to a fine tuning of electrode position in the majority of cases. Collaboration between neurosurgeon, neurophysiologist and neuroanesthesiologist is crucial, since slight modifications of sedation level can impact profoundly on MER reliability.

Impact of optimized transcutaneous auricular vagus nerve stimulation on cardiac autonomic profile in healthy subjects and heart failure patients.

Objective.To determine the optimal frequency and site of stimulation for transcutaneous vagus nerve stimulation (tVNS) to induce acute changes in the autonomic profile (heart rate (HR), heart rate variability (HRV)) in healthy subjects (HS) and patients with heart failure (HF).Approach.We designed three single-blind, randomized, cross-over studies: (1) to compare the acute effect of left tVNS at 25 Hz and 10 Hz (n= 29, age 60 ± 7 years), (2) to compare the acute effect of left and right tVNS at the best frequency identified in study 1 (n= 28 age 61 ± 7 years), and (3) to compare the acute effect of the identified optimal stimulation protocol with sham stimulation in HS and HF patients (n= 30, age 59 ± 5 years, andn= 32, age 63 ± 7 years, respectively).Main results.In study 1, left tragus stimulation at 25 Hz was more effective than stimulation at 10 Hz in decreasing HR (-1.0 ± 1.2 bpm,p< 0.001 and -0.5 ± 1.6 bpm, respectively) and inducing vagal effects (significant increase in RMSSD, and HF power). In study 2, the HR reduction was greater with left than right tragus stimulation (-0.9 ± 1.5 bpm,p< 0.01 and -0.3 ± 1.4 bpm, respectively). In study 3 in HS, left tVNS at 25 Hz significantly reduced HR, whereas sham stimulation did not (-1.1 ± 1.2 bpm,p< 0.01 and -0.2 ± 2.9 bpm, respectively). In HF patients, both active and sham stimulation produced negligible effects.Significance.Left tVNS at 25 Hz is effective in acute modulation of cardiovascular autonomic control (HR, HRV) in HS but not in HF patients (NCT05789147).

Radiological and intraoperative findings of a rare case of vestibular paroxysmia.

Vestibular paroxysmia (VP) is a rare condition. The pathogenesis is linked to a neurovascular conflict (NVC) between an abnormal arterial loop and the VII/VIII cranial nerve complex in the cerebello-pontine angle. Due to its rarity, intraoperative findings are only anecdotally reported. Here we reported on a case of VP, showing the radiological images and the intraoperative surgical video of microvascular decompression (MVD). Further we discussed our findings considering the pertinent literature. We think that in case of VP the concordance between the side of tinnitus/hypoacusia and the side of NVC on magnetic resonance imaging should be always looked for before considering MVD as a therapeutic option.

A systematic review on the efficacy of adjunctive surgical strategies during microvascular decompression for trigeminal neuralgia without intraoperative evidence of neurovascular conflict.

Aim of the present study was to conduct a comprehensive review of surgical strategies that can be offered to patients with trigeminal neuralgia undergoing microvascular decompression (MVD) surgery and without intraoperative evidence of neurovascular conflict, with a high pre-operative suspicion of conflict lacking intraoperative confirmation, or individuals experiencing recurrence after previous treatment. This systematic review followed established guidelines (PRISMA) to identify and critically appraise relevant studies. The review question was formulated according to the PICO (P: patients; I: intervention; C: comparison; O: outcomes) framework as follows. For patients with trigeminal neuralgia (P) undergoing MVD surgery (I) without demonstrable preoperative neurovascular conflict, high suspicion of conflict but no intraoperative confirmation or recurrence after previous treatment (C), do additional surgical techniques (nerve combing, neurapraxia, arachnoid lysis) (O) improve pain relief outcomes (O)? The search of the literature yielded a total of 221 results. Duplicate records were then removed (n = [76]). A total of 143 papers was screened, and 117 records were excluded via title and abstract screening; 26 studies were found to be relevant to our research question and were assessed for eligibility. Upon full-text review, 17 articles were included in the review, describing the following techniques; (1) internal neurolysis (n = 6) (2) arachnoid lysis/adhesiolysis (n = 2) (3) neurapraxia (n = 3) (4) partial rhizotomy of the sensory root (n = 4) (5) pontine descending tractotomy (n = 2). The risk of bias was assessed using the ROBINS-I (Risk of Bias in Non-randomized Studies - of Interventions) assessment tool. While the described techniques hold promise, further research is warranted to establish standardized protocols, refine surgical approaches, and comprehensively evaluate long-term outcomes.

Bleeding and thrombotic events and intensity of heparin therapy in the two first waves of COVID-19.

A systemic inflammatory response occurs during SARS-CoV2 infection and is associated with hypercoagulability and thrombotic events. From March 2020 in our hospital different dosages of low-molecular weight heparin (LMWH) were introduced according to the level of patient care intensity. Because bleeding episodes occurred in hospitalized COVID-19 patients on heparin, the dosage of LMWH at the end of first wave was tailored on the severity of COVID-19. The aim of this study is to describe bleeding and thrombotic events in patients hospitalized with SARS-CoV2 infection on LMWH therapy in the two waves of COVID-19 and analyze the factors associated with these events. Among 1143 patients enrolled in the COVID-19 Network registry, 912 were included in the analysis, 537 of them admitted during the first wave and 375 during the second. Bleeding events were 30 (3.3%): 22 (2.4%) major and 8 (0.9%) non-major. Arterial and venous thrombotic events were 6 (0.7%) and 24 (2.6%). The incidence of venous thrombotic events was higher in the first than in the second wave (0.29% [95% CI 0.20-0.45] events/day vs. 0.05% [95% CI 0.02-0.16]), with a 71% risk reduction (95% CI 22%-94%). The incidence of bleeding was 0.33% (95% CI 0.22-0.50) vs 0.14% events/day (95% CI 0.07-0.28), with no statistical between-wave difference (HR 0.41 95% CI 0.16-1.08). After adjusting for the competing risks of death and comorbidities, patients in the second wave had lower odds to have thrombotic events than in the first wave (0.24 HR [95% C.I. 0.07-0.89]). In this retrospective study on COVID-19 we found a low rate of hemorrhagic and thrombotic events, that may be explained by the absence in the case material of patients admitted to intensive care unit.

The "state of the art" of intraoperative neurophysiological monitoring: An Italian neurosurgical survey.

Introduction: Intraoperative Neurophysiological Monitoring (IOM) is widely used in neurosurgery but specific guidelines are lacking. Therefore, we can assume differences in IOM application between Neurosurgical centers. Research question: The section of Functional Neurosurgery of the Italian Society of Neurosurgery realized a survey aiming to obtain general data on the current practice of IOM in Italy. Materials and methods: A 22-item questionnaire was designed focusing on: volume procedures, indications, awake surgery, experience, organization and equipe. The questionnaire has been sent to Italian Neurosurgery centers. Results: A total of 54 centers completed the survey. The annual volume of surgeries range from 300 to 2000, and IOM is used in 10-20% of the procedures. In 46% of the cases is a neurologist or a neurophysiologist who performs IOM. For supra-tentorial pathology, almost all perform MEPs (94%) SSEPs (89%), direct cortical stimulation (85%). All centers perform IOM in spinal surgery and 95% in posterior fossa surgery. Among the 50% that perform peripheral nerve surgery, all use IOM. Awake surgery is performed by 70% of centers. The neurosurgeon is the only responsible for IOM in 35% of centers. In 83% of cases IOM implementation is adequate to the request. Discussion and conclusions: The Italian Neurosurgical centers perform IOM with high level of specialization, but differences exist in organization, techniques, and expertise. Our survey provides a snapshot of the state of the art in Italy and it could be a starting point to implement a consensus on the practice of IOM.

Impact of electronic cigarettes (e-cigs) and heat-not-burn/heated tobacco products (HnB/HTP) on asthma and chronic obstructive pulmonary disease: a viewpoint of the Italian Society of Internal Medicine.

The association of cigarette smoking with several severe and very severe diseases (oncological, cardiovascular, respiratory) which have dramatic epidemiological, medical, and financial impact, is a well-known public threat. Asthma and chronic obstructive pulmonary disease (COPD) are highly prevalent diseases in Italy, posing significant public health challenges. Tobacco smoking, a primary risk factor for COPD and a common asthma trigger, remains a critical preventable public health issue. While universally acknowledged that quitting smoking drastically reduces the risk of smoking-related health issues, a significant portion of smokers and patients find quitting challenging or undesirable, hence a need for new ways to deal with it. A worth considering alternative might be the switch to electronic cigarettes (e-cig), and heat-not-burn/heated tobacco products (HnB/HTP). Emerging evidence suggests potential benefits in asthma and COPD management when transitioning from traditional smoking to e-cigs or HnB devices. However, the effectiveness of these products in facilitating smoking cessation is still debated, alongside concerns about their role in promoting smoking initiation among non-smokers. Internists are among the physicians who most frequently assist patients with smoking-related diseases, and in this perspective they cannot avoid paying attention to the progressive diffusion of smoking products alternative to the traditional cigarette, and to the controversies with respect to their use. In this context, the Italian Society of Internal Medicine, also recognizing a growing need for clarity for healthcare providers, has undertaken a comprehensive analysis of existing literature to offer an informed perspective on the health impact of e-cigs and HnB/HTP on asthma and COPD.

Unsatisfactory Neurological Outcome in an Intramedullary Thoracic Intermediate-Grade Melanocytoma-Systematic Review and Illustrative Case.

BACKGROUND: Intramedullary melanocytomas are exceedingly rare, with only twenty-four cases reported up to now. They present as local invasive tumors despite their benign biological behavior. Attempting a complete safe resection often results in severe post-operative neurological deficits, as in our case presented here. METHODS: A systematic review was conducted across the PubMed and Scopus databases including studies published till February 2024. RESULTS: A total of 19 studies were included, encompassing 24 cases. A similar distribution between sexes was noted (M:F 13:11), with ages ranging from 19 to 79 years. The thoracic segment was most affected, and intermediate-grade melanocytoma (19 cases) was the most common histotype. Radiographically, intramedullary melanocytomas usually appear as hyperintense hemorrhagic lesions peripheral to the central canal with focal nodular enhancement. Intraoperatively, they are black-reddish to tan and are tenaciously adherent lesions. In the sampled studies, IONM employment was uncommon, and post-operative new-onset neurological deficits were described in 16 cases. Adjuvant RT was used in four cases and its value is debatable. Recurrence is common (10 cases), and adjuvant therapies (RT or repeated surgery) seem to play a palliative role. CASE PRESENTATION: A 68-year-old woman presented with a three-year history of worsening spastic paraparesis and loss of independence in daily activities (McCormick grade 4). An MRI revealed an intramedullary tumor from Th5 to Th7, characterized by T1-weighted hyperintensity and signs of recent intralesional hemorrhage. Multimodal neuromonitoring, comprising the D-Wave, guided the resection of a black-tan-colored tumor with hyper-vascularization and strong adherence to the white matter. During final dissection of the lesion to obtain gross total resection (GTR), a steep decline in MEPs and D-Wave signals was recorded. Post-operatively, the patient had severe hypoesthesia with Th9 level and segmental motor deficits, with some improvement during neurorehabilitation. Histopathology revealed an intermediate-grade melanocytoma (CNS WHO 2021 classification). A four-month follow-up documented the absence of relapse. CONCLUSIONS: This literature review highlights that intramedullary T1 hyperintense hemorrhagic thoracic lesions in an adult patient should raise the suspicion of intramedullary melanocytoma. They present as locally aggressive tumors, due to local invasiveness, which often lead to post-operative neurological deficits, and frequent relapses, which overwhelm therapeutic strategies leading to palliative care after several years.

H3K27-Altered Diffuse Glioma of the Spinal Cord in Adult Patients: A Qualitative Systematic Review and Peculiarity of Radiological Findings.

Background: Primary spinal cord diffuse gliomas (SpDG) are rare tumors that may harbor, like diffuse intrinsic pontine gliomas (DIPG), H3K27M mutations. According to the WHO (2021), SpDGs are included in diffuse midline H3K27-altered gliomas, which occur more frequently in adults and show unusual clinical presentation, neuroradiological features, and clinical behavior, which differ from H3 G34-mutant diffuse hemispheric glioma. Currently, homogeneous adult-only case series of SpDG, with complete data and adequate follow-up, are still lacking. Methods: We conducted a qualitative systematic review, focusing exclusively on adult and young adult patients, encompassing all studies reporting cases of primitive, non-metastatic SpDG with H3K27 mutation. We analyzed the type of treatment administered, survival, follow-up duration, and outcomes. Results: We identified 30 eligible articles published between 1990 and 2023, which collectively reported on 62 adult and young adult patients with primitive SpDG. Postoperative outcomes were assessed based on the duration of follow-up, with outcomes categorized as either survival or mortality. Patients who underwent surgery were followed up for a mean duration of 17.37 months, while those who underwent biopsy had a mean follow-up period of 14.65 months. Among patients who were still alive, the mean follow-up duration was 18.77 months. The radiological presentation of SpDG varies widely, indicating its lack of uniformity. Conclusion: Therefore, we presented a descriptive scenario where SpDG was initially suspected to be a meningioma, but was later revealed to be a malignant SpDG with H3K27M mutation.

Predominant cardiac sympathetic modulation during wake and sleep in patients with Rett syndrome.

BACKGROUND: Rett syndrome (RTT) is a rare neurological disorder primarily associated with mutations in the methyl-CpG-binding protein 2 (MECP2) gene. The syndrome is characterized by cognitive, social, and physical impairments, as well as sleep disorders and epilepsy. Notably, dysfunction of the autonomic nervous system is a key feature of the syndrome. Although Heart Rate Variability (HRV) has been used to investigate autonomic nervous system dysfunction in RTT during wakefulness, there is still a significant lack of information regarding the same during sleep. Therefore, our aim was to investigate cardiovascular autonomic modulation during sleep in subjects with RTT compared to an age-matched healthy control group (HC). METHOD: A complete overnight polysomnographic (PSG) recording was obtained from 11 patients with Rett syndrome (all females, 10 ± 4 years old) and 11 HC (all females, 11 ± 4 years old; p = 0.48). Electrocardiogram and breathing data were extracted from PSG and divided into wake, non-REM, and REM sleep stages. Cardiac autonomic control was assessed using symbolic non-linear heart rate variability analysis. The symbolic analysis identified three patterns: 0 V% (sympathetic), 2UV%, and 2LV% (vagal). RESULTS: The 0 V% was higher in the RTT group than in the HC group during wake, non-REM, and REM stages (p < 0.01), while the 2LV and 2UV% were lower during wake and sleep stages (p < 0.01). However, the 0 V% increased similarly from the wake to the REM stage in both RTT and HC groups. CONCLUSIONS: Therefore, the sympatho-vagal balance shifted towards sympathetic predominance and vagal withdrawal during wake and sleep in RTT, although cardiac autonomic dynamics were preserved during sleep.

Ivabradine restores tonic cardiovascular autonomic control and reduces tachycardia, hypertension and left ventricular inflammation in post-weaning protein malnourished rats.

Malnutrition results in autonomic imbalance and heart hypertrophy. Overexpression of hyperpolarization-activated cyclic nucleotide-gated channels (HCN) in the left ventricles (LV) is linked to hypertrophied hearts and abnormal myocardium automaticity. Given that ivabradine (IVA) has emerging pleiotropic effects, in addition to the widely known bradycardic response, this study evaluated if IVA treatment could repair the autonomic control and cardiac damages in malnourished rats. AIM: Assess the impact of IVA on tonic cardiovascular autonomic control and its relationship with hemodynamics regulation, LV inflammation, and HCN gene expression in post-weaning protein malnutrition condition. MAIN METHODS: After weaning, male rats were divided into control (CG; 22 % protein) and malnourished (MG; 6 % protein) groups. At 35 days, groups were subdivided into CG-PBS, CG-IVA, MG-PBS and MG-IVA (PBS 1 ml/kg or IVA 1 mg/kg) received during 8 days. We performed jugular vein cannulation and electrode implant for drug delivery and ECG registration to assess tonic cardiovascular autonomic control; femoral cannulation for blood pressure (BP) and heart rate (HR) assessment; and LV collection to evaluate ventricular remodeling and HCN gene expression investigation. KEY FINDINGS: Malnutrition induced BP and HR increases, sympathetic system dominance, and LV remodeling without affecting HCN gene expression. IVA reversed the cardiovascular autonomic imbalance; prevented hypertension and tachycardia; and inhibited the LV inflammatory process and fiber thickening caused by malnutrition. SIGNIFICANCE: Our findings suggest that ivabradine protects against malnutrition-mediated cardiovascular damage. Moreover, our results propose these effects were not attributed to HCN expression changes, but rather to IVA pleiotropic effects on autonomic control and inflammation.

Clinical research on extreme longevity: The FACET experience.

People with extreme longevity represent a unique model to study the biology of aging. Unfortunately, their inclusion in research projects is challenging with the consequent lack of evidence and the need to rely on small convenience samples. Given the growing global aging population, especially in the segment of the oldest old (i.e., aged 90 and older), research in this population has become crucial. Furthermore, by studying the characteristics of extremely longeval persons, it might be possible to 1) better understand the mechanisms of aging, and 2) identify endogenous or exogenous factors contributing to a long life. The design and implementation of research activities in the oldest people need special consideration and a pragmatic approach. Possible implementable solutions and suggestions are provided from experience gained during the conduction of the FAtigue in CEnTenarians (FACET) study.