Repetitive Transcranial Magnetic Stimulation of the Human Motor Cortex Modulates Processing of Heat Pain Sensation as Assessed by the Offset Analgesia Paradigm.

Offset analgesia (OA), which is defined as a disproportionately large reduction in pain perception following a small decrease in a heat stimulus, quantifies temporal aspects of endogenous pain modulation. In this study on healthy subjects, we aimed to (i) determine the Heat Pain Threshold (HPT) and the response to constant and dynamic heat stimuli assessing sensitization, adaptation and OA phenomena at the thenar eminence; (ii) evaluate the effects of high-frequency repetitive Transcranial Magnetic Stimulation (rTMS) of the primary motor cortex (M1) on these measures. Twenty-four healthy subjects underwent quantitative sensory testing before and after active or sham 10 Hz rTMS (1200 stimuli) of the left M1, during separate sessions. We did not observe any rTMS-related changes in the HPT or visual analogue scale (VAS) values recorded during the constant trial. Of note, at baseline, we did not find OA at the thenar eminence. Only after active rTMS did we detect significantly reduced VAS values during dynamic heat stimuli, indicating a delayed and attenuated OA phenomenon. rTMS of the left M1 may activate remote brain areas that belong to the descending pain modulatory and reward systems involved in the OA phenomenon. Our findings provide insights into the mechanisms by which rTMS of M1 could exert its analgesic effects.

Age-, gender- and body site-specific reference values of thermal Quantitative Sensory Testing in the Italian population using the Q-sense device.

BACKGROUND: Age-, gender- and body site-specific values of thermal Quantitative Sensory Testing (QST) measures have not yet been reported using the novel and cheap device 'Q-sense'. Here, we aimed to assess normative values of Q-sense-derived parameters in a representative Italian population. METHODS: QST parameters were measured in 84 healthy participants (42 males; aged 20-76 years) equally distributed into three age groups (18-39, 40-59 and 60-80 years). We explored the Warm and the Cold Detection Thresholds (WDT and CDT, respectively) with the method of limits (MLI) and the method of levels (MLE), and the Heat Pain Threshold (HPT) with the MLI. We tested the trigeminal supraorbital region, the hand thenar, and the foot dorsum on the right body side. RESULTS: We calculated non-parametric reference limits (2.5-97.5th) according to age, gender and tested site. All QST measures were affected by age, gender and tested site. In the extra-trigeminal body sites, females showed lower WDT and higher CDT, while males had higher HPT. Worse sensory discriminative abilities and increased HPT values were found in people aged over 40 on the foot. Age-related differences were more evident with the reaction time-dependent MLI vs. MLE paradigm. CONCLUSIONS: Demographic characteristics must be considered when QST is used in the clinical setting. The definition of reference limits for sensory testing with the Q-sense herein provided can pave the way towards a more widespread use of thermal QST for diagnosing small fiber neuropathy and for identifying patients' profiles in different chronic pain syndromes.

Electrophysiological evidence of subclinical trigeminal dysfunction in patients with COVID-19 and smell impairment: A pilot study.

Background: Smell and taste disturbances are among the most frequent neurological symptoms in patients with COVID-19. A concomitant impairment of the trigeminal nerve has been suggested in subjects with olfactory dysfunction, although it has not been confirmed with objective measurement techniques. In this study, we explored the trigeminal function and its correlations with clinical features in COVID-19 patients with impaired smell perception using electrophysiological testing. Methods: We enrolled 16 consecutive patients with mild COVID-19 and smell impairment and 14 healthy controls (HCs). Olfactory and gustatory symptoms were assessed with self-reported questionnaires. Electrophysiological evaluation of the masseter inhibitory reflex (MIR) and blink reflex (BR) was carried out to test the trigeminal function and its connections within the brainstem. Results: Masseter inhibitory reflex (MIR) analysis revealed higher latency of ipsilateral and contralateral early silent period in patients when compared with HCs. No significant differences between groups were detected as regards the duration of the early and late silent period. However, several patients showed a prolonged duration of the early silent period. BR evaluation disclosed only an increased amplitude of early components in patients. Conclusions: Patients with COVID-19 and smell impairment show a subclinical trigeminal nerve impairment. Trigeminal alterations mainly involve the oligosynaptic pathway, as a result of either direct viral damage or secondary neuroinflammation of the peripheral trigeminal fibers, whereas the polysynaptic ponto-medullary circuits seem to be spared. The prolonged duration of the early silent period and the increased amplitude of early BR response might reflect a compensatory upregulation of the trigeminal function as a consequence of the olfactory dysfunction.

Novel three-dimensional acellular dermal matrix for prepectoral breast reconstruction: First year in review with BRAXON® Fast.

Implant-based breast reconstruction is part of breast cancer treatment, and increasingly optimized reconstructive procedures exploit highly biocompatible materials to ensure enhanced aesthetic-functional results. Acellular dermal matrices (ADMs) are collagen-based materials that made prepectoral implant placement possible, thanks to their bioactive antifibrosis action. Recently, the first three-dimensional ADM, BRAXON® Fast, has been produced. Its 3D design represents the technological evolution of BRAXON® ADM, a flat collagen matrix, and allows for a time-saving complete wrapping of the synthetic prosthesis, thus creating a total biological interface on the implant with patient's tissues. Here, we report our experience on the first 23 eligible patients who received BRAXON® Fast-assisted prepectoral reconstruction. On a total of 27 breasts, the overall complication rate was 11.1%, including one minor seroma (3.7%), one case of necrosis (3.7%), and one implant removal due to infection. As new-generation devices, 3D ADMs showed an effective performance, allowing to reduce the overall exposure time for implant preparation and providing an optimal safety profile.

Microsurgical Reconstruction of the Nose: The Aesthetic Approach to Total Defects.

BACKGROUND: Reconstruction of complex defects involving nose and close facial units represents an aesthetic and functional challenge. Restoring satisfactory nasal shape, combining aesthetic, nasal function and patent airways is mandatory. In this paper, we describe our approach to total nose defects and we report our 20-year experience in microvascular nose reconstruction.Clinical cases are shown to illustrate different surgical techniques and the evolution of our approach. METHODS: Nasal reconstruction procedures were performed on 21 patients between 2000 and 2020 using the radial forearm flap (RFF) or anterolateral thigh (ALT) flap. Reported reconstructions included total/subtotal nasal defects, caused by cancer resections. The key point of our approach is the expanded forehead flap for skin coverage. Reconstruction is completed by cartilage grafts to restore nasal framework and to shape nasal tip. Ancillary procedures were needed in some cases to optimize aesthetic outcomes. RESULTS: Twenty-one patients completed the multistage nasal reconstruction. The RFF flap was used in 56% of the cases (n = 11), while the ALT flap was used in 44% (n = 10) of our case series. No difference has been detected in the number of reconstructive stages required to achieve the final result comparing RFF and ALT reconstruction (3.3 vs. 3.1 reconstructive steps). Ancillary procedures were performed in 7 patients. CONCLUSION: Microvascular tissue transfer plays a key role in full-thickness nasal defects restoration. Comparing the two groups, both the RFF and ALT are effective and reliable options in lining reconstruction, although with different indications. Expanded forehead flap, combined to free cartilage graft, is our gold standard to provide external skin coverage to rebuild the nasal framework. According to our current approach, accurate preoperative planning, supported by modern technologic tools, multistage reconstruction, and ancillary procedures are useful to accomplish satisfactory functional and aesthetic outcomes.

Cutaneous metastases of prostatic adenocarcinoma in two dogs.

Canine prostatic adenocarcinoma is an aggressive malignancy characterized by rapid growth, local invasiveness, and early metastatic spread. Metastases of prostatic cancer are generally diffuse at the time of diagnosis due to hematogenous or lymphatic spread and by direct exfoliation of neoplastic cells into the peritoneal cavity. Here we describe two dogs with prostatic adenocarcinoma and skin metastases. The first was a 12-year-old intact male German Shepherd dog that was presented with a history of chronic prostatic disease and multiple skin nodules that recently appeared on the ventral abdomen. The second was an 8-year-old intact male mixed breed dog that was referred for a neurologic examination because of a 1-month history of back pain and kyphosis of undefined origin. Cutaneous cytology of the first case was suggestive of carcinoma, and at necropsy, prostatic adenocarcinoma with metastases to the skin, spleen, liver, pancreas, kidneys, and lungs were found. In the second case, a computed tomographic examination revealed a prostatic neoplasm with inguinal, subcutaneous, and cutaneous nodular metastases. Cytology and histopathology were suggestive of primary prostatic adenocarcinoma with cutaneous and subcutaneous metastases. To the authors' knowledge, these are the first reported cases of prostatic adenocarcinoma skin metastases in dogs with cytologic descriptions.

The "ART" of facial filler injections: Avoid, recognize, and treat hyaluronic acid-induced complications.

BACKGROUND: Hyaluronic acid (HA) fillers are frequently used for cosmetic purposes as volumizers or as wrinkle fillers. One of the major advantages of hyaluronic acid use is the possibility to neutralize it by using hyaluronidase should complications occur. PATIENT: A case of a 21-year-old female patient is presented, in whom a hyaluronic acid injection-induced vascular occlusion was seen four days after the initial injection, with increasing pain and severe signs of ischemia. METHOD: Treatment consisted of an immediate hyaluronidase injection, supplemented with administration of acetylsalicylic acid, piracetam, low molecular weight heparin (LMWH), corticosteroids, analgesics, prophylactic antibiotics, application of topical nitroglycerin and warmth, smoking cessation, and hyperbaric oxygen therapy. RESULTS: The initial progress and evolution of the deformity with possible therapeutic options are being discussed. CONCLUSION: The "ART" (avoid, recognize, and treat) in handling filler complications is presented, as a new universal guideline for clinical aesthetic practitioners and injectors.

Effect of early correction of nasal septal deformity in unilateral cleft lip and palate on inferior turbinate hypertrophy and nasal patency.

OBJECTIVES: A relatively neglected aspect of cleft lip nasal deformity is the effect of septal deviation and inferior turbinate hypertrophy (ITH) on the functional airway. In particular, ITH in the noncleft side can be especially problematic, because it reduces the healthy nasal area, creating bilateral nasal obstruction that might affect the growth of the maxillofacial skeleton. Although these anatomic and functional changes are documented, few recommendations have been developed regarding the proper approach to ITH. The aim of the present study was to asses the ITH severity and determine the degree of nasal airway patency in patients who have undergone primary correction of the nasal septum during lip repair compared to patients operated on without primary septal correction. METHODS: The study population included two groups. One group consisted of twenty unilateral cleft lip palate UCLP patients who have previously undergone primary rhinoseptoplasty as part of their treatment plan. The control group consisted of twenty UCLP patients operated on without rhinoseptal correction. The Nasal Obstructive Symptom Evaluation (NOSE) scale and nasal endoscopy were used to assess nasal obstruction. RESULTS: The overall untreated group reported severe symptoms across all NOSE scale dimensions more frequently than children who have undergone primary rhinoseptoplasty. The difference was statistically significant for each dimensions (p < 0.05). The mean NOSE score for group A and group B was 21.4 ±â€¯9.4 and 70.8 ±â€¯17.2 respectively (p < 0.0001). In group A turbinate size decreased significantly (p < 0.05) compared to pre-operative data. Comparing the two groups a statistically significant difference in turbinate size was observed (p < 0.0001). CONCLUSION: The results of the present study confirm that there is a significant degree of ITH and nasal airway dysfunction in patients with UCLP. Early septal repositioning during primary cleft lip repair results in a statistically significant reduction in IT size and improvement of nasal patency.

Osteomyocutaneous fibular flap harvesting: Computer-assisted planning of perforator vessels using Computed Tomographic Angiography scan and cutting guide.

INTRODUCTION: Mandibular reconstruction performed after virtual planning has become more common during recent years. The gold standard for extensive mandibular reconstruction is of course a fibular free flap. In designing an osteomyocutaneous fibula flap, poor planning, aberrant anatomy and/or inadequate perforator vessels are the most frequent causes of complications and may force the surgeon to modify the flap design, explore the contralateral leg or harvest an additional microvascular flap. The goal of our study was to pre-operatively evaluate the vascular anatomy of the fibula and localize the cutaneous perforator vessels, so to create the fibular cutting guide based on the position of the cutaneous perforator and safely harvest the reconstructive flap. MATERIALS AND METHODS: Twenty consecutive patients who were candidates for mandibular reconstruction using a fibular microvascular free flap were enrolled in this study between January 2016 and August 2016. The patients were preoperatively assessed with a Computed Tomographic scan of head and neck and with a Computed Tomographic Angiography (CTA) scan of the lower limbs to evaluate the vascular anatomy of the fibula. Virtual planning was carried out for all patients. The fibular cutting guide was based on the position of the perforator cutaneous vessels, which were used to harvest the cutaneous part of the flap. Preoperative CT measurements were performed in order to identify the cutaneous perforators on the patients' skin. Intraoperative checking was performed to evaluate the accuracy of the perforators' position and the reproducibility of the virtual planning. RESULTS: In 5 patients out of 20 (25%), anatomical anomalies were discovered, without clinical evidence. The perforator vessels were localized in all patients. The average difference between the CTA and the intraoperative perforator localization was 1 mm (range 0-2 mm). Fibular cutting guide was positioned and fitted the anatomy of the patients in all treated patients. This allowed us to perform the planned segmentation of the fibula, obtaining the correct number of segments. In all cases, flap insetting was carried out and skin paddle was positioned as preoperatively planned. Neither donor site complications nor flap complications occurred. CONCLUSIONS: Preoperative evaluation of the legs using CTA, in patients who undergo an osteomyocutaneous fibular free flap for mandibular reconstruction, is a valuable approach to reduce altered-anatomy related complications and to improve the accuracy and outcomes of the reconstruction, especially in reconstructions of complex defects. In these cases, a soft tissue-based cutting guide can be planned based on the perforator vessels of the skin paddle, minimizing the harvesting risks of vascular lesions. Further studies and longer follow-ups are needed to evaluate the long-term outcomes and advantages of this procedure.

Universal cranial ultrasound screening in preterm infants with gestational age 33-36 weeks. A retrospective analysis of 724 newborns.

BACKGROUND: Cranial ultrasonography is a useful tool to detect intracranial lesions in premature neonates at risk. Our primary aim was to determine the number of patients with abnormal cranial ultrasonography. Secondary aims were to evaluate the usefulness of universal cranial ultrasonography screening in moderately preterm infants. METHODS: All infants born from 2007 to 2012 at the University Hospital of Ferrara (Italy), with gestational age of 33-36 weeks, were included in the study. Cranial ultrasonography findings were retrospectively classified into nonsignificant and significant. RESULTS: All the 724 babies born were screened. Intracranial lesions were in 13% of neonates (3.7% at 36 weeks to 27.1% at 33 weeks of gestational age). Babies born at 33-34 weeks of gestational age were four times more likely to have an abnormal cranial ultrasonography than those at 35-36 weeks. Statistical analysis revealed no association between cranial ultrasonography abnormalities and being small for gestational age or mode of delivery. A significant association was present between the presence of head circumference less than the third percentile, the need for ventilation or surfactant, low Apgar index at fifth minute, and neurological abnormalities. The presence of at least one considered risk factor increases the probability of cranial ultrasonography abnormalities twice in infants born at 33-34 weeks and 15 times in born at 35-36 weeks. CONCLUSIONS: A considerable number of infants born between 33 and 36 weeks have cranial ultrasonography abnormalities. We suggest that screening should be performed or at least that a uniform protocol should be developed for the early detection of all significant cranial ultrasonography abnormalities.

Breast-milk characteristics protecting against allergy.

Breast milk and colostrum are the first feeding sources for a child, providing nutrients, growth factors and immunological components, which are crucial for the newborn's correct development and health. Length of exclusive breastfeeding and time of solid foods introduction is a key factor that may influence allergy development. There is an emerging evidence of a relationship between breastfeeding, milk composition and lower risk of chronic diseases, such as diabetes, obesity, hypertension and allergies. This review examines current evidence regarding humoral and cellular characteristics of breast-milk, and potential role of environment, maternal diet and breastfeeding on the allergy development in children.

Chronic eosinophilic leukemia in a cat: cytochemical and immunophenotypical features.

A 3-year-old, male, domestic shorthaired cat was presented with a 3-day history of anorexia and depression. The cat was moderately dehydrated, had pale, slightly icteric, mucous membranes, oral ulcerations, and mild hepatosplenomegaly. A feline leukemia virus (FeLV) antigen test was positive. CBC results obtained at initial presentation included severe normocytic, normochromic, nonregenerative anemia, severe thrombocytopenia, and marked leukocytosis (>100,000/microL) with 77% eosinophils. After 15 days of treatment with prednisone and doxycycline, the cat had persistent severe nonregenerative anemia (HCT 3.4%), thrombocytopenia (28,000/microL), and extreme eosinophilia (total eosinophils, 123.1 x 10(3)/microL; segmented 103.0 x 10(3)/microL; immature 20.1 X 10(3)/microL). Cytologic examination of aspirates from bone marrow, liver, lymph nodes, and spleen revealed a predominance of mature and immature eosinophils, many with dysplastic changes. The M:E ratio was 96.4. On histopathologic examination, multiple organs were infiltrated by eosinophilic granulocytes. Neoplastic cells in blood and bone marrow stained positive for alkaline phosphatase and were negative for myeloperoxidase, chloroacetate esterase, and alpha-naphthyl acetate esterase. On flow cytometric analysis of peripheral blood, the neoplastic cells were positive for CD11b and CD14. These findings were consistent with chronic eosinophilic leukemia. To our knowledge, this is the first report of chronic eosinophilic leukemia in a cat associated with naturally acquired FeLV infection, in which flow cytometry was used to characterize the neoplastic cells.

Canine angiosarcoma: cytologic, histologic, and immunohistochemical correlations.

BACKGROUND: Angiosarcomas (AS) are malignant tumors that arise from vascular endothelial cells and are common in dogs. Histologically, AS are markedly heterogeneous neoplasms that make interpretation by cytology difficult. OBJECTIVE: Our objective was to evaluate the cytologic features of canine AS and look for additional diagnostic criteria. METHODS: Cytologic specimens from 19 histologically and immunohistochemically confirmed cases of canine AS were extensively reviewed for cytologic features. We compared cytologic, histopathologic, and immunohistochemical findings. RESULTS: Neoplastic cells in 14 cytology specimens had a high-grade sarcomatous appearance, whereas in 4 specimens the cells were extremely pleomorphic, ranging from sarcomatous to epithelioid. In the remaining case, the neoplastic cells were low grade, spindle shaped, and monomorphic. Other relevant cytologic findings were blood contamination (18/19 cases), cellular cohesiveness (16/19), punctate cytoplasmic vacuolation (19/19), background neutrophilia (11/19) and eosinophilia (5/19), erythrophagocytosis (8/19), extramedullary hematopoiesis (8/19), and apoptotic leukocytes (14/19). Vasoformative features (ie, pseudoacinar structures) were observed in 7 of 19 samples. Histologically, 16 neoplasms had a proliferative pattern typical of well-differentiated canine AS. Three tumors were atypical poorly differentiated AS; 2 of these had a striking epithelioid pattern and 1 was a poorly differentiated spindle cell tumor with focal vascular differentiation. Immunohistochemically, tumor cells in 16 cases were positive for both endothelial markers tested (Factor VIII-related antigen [FVIII-ra] and CD31 antigen), 2 were positive for CD31 only, and 1 was positive for FVIII-ra only. The epithelioid AS were negative for cytokeratins. CONCLUSIONS: The cytologic characteristics of canine AS are widely heterogeneous, but supplementary findings can provide clues that are useful for making a cytologic diagnosis. Histologic and immunohistochemical confirmation is nonetheless warranted in all cases.