Temperature is an essential oceanographic variable (EOV) that still today remains coarsely resolved below the surface and near the seafloor. Here, we gather evidence to confirm that Distributed Acoustic Sensing (DAS) technology can convert tens of kilometer-long seafloor fiber-optic telecommunication cables into dense arrays of temperature anomaly sensors having millikelvin (mK) sensitivity, thus allowing to monitor oceanic processes such as internal waves and upwelling with unprecedented detail. Notably, we report high-resolution observations of highly coherent near-inertial and super-inertial internal waves in the NW Mediterranean sea, offshore of Toulon, France, having spatial extents of a few kilometers and producing maximum thermal anomalies of more than 5 K at maximum absolute rates of more than 1 K/h. We validate our observations with in-situ oceanographic sensors and an alternative optical fiber sensing technology. Currently, DAS only provides temperature changes estimates, however practical solutions are outlined to obtain continuous absolute temperature measurements with DAS at the seafloor. Our observations grant key advantages to DAS over established temperature sensors, showing its transformative potential for the description of seafloor temperature fluctuations over an extended range of spatial and temporal scales, as well as for the understanding of the evolution of the ocean in a broad sense . Diverse ocean-oriented fields could benefit from the potential applications of this fast-developing technology. On climatic timescales, deep temperature measurements are needed to constrain the global ocean heat content and imbalance3, to monitor the evolution of water masses on regional scales4, climate changes5 and to predict the chemical6 and biological7 evolution of the ocean. Improved seafloor measurements within the coastal domain are much needed given their poor representation in climatic models8. At timescales of hours to minutes, ocean temperature variability is related to the internal wavefield and bottom boundary turbulent activity which affect the circulation of nutriments in the nearshore available to sustain marine life10, the propagation of hydroacoustic waves11 and the vertical mixing of the ocean at different scales12. The bottom boundary layer dynamics also remains an area of forefront research in both the coastal domain14 and the abyss16.Monitoring seafloor ocean temperature variability became a priority over the last years within the Oceanographic community17.In-situ ocean thermometry typically relies on scattered point measurements and temporary deployments near the water surface , which tend to be limited in terms of temporal and/or spatial resolution, while access to the deep ocean and remote regions remains challenging. Oceanographic moorings, Autonomous Underwater Vehicles, i.a. are attempting to fill this gap. However, obtaining a wide spatial coverage and long-term continuous measurements below the water surface and near the seafloor remains difficult19. Among these, Distributed Acoustic Sensing (DAS) has gained wide interest thanks to its ability to monitor seismo-acoustic signals and dynamic strain with high sensitivity21, making it suitable for a wide range of geophysical monitoring applications32. Specifically, DAS systems rely on the analysis of the Rayleigh back-scattering spectrum of light. For some basics on DAS working principles, the reader is referred to the Supplementary Text In recent years, efforts have been devoted to transform fiber-optic cables into dense arrays of sensors with technologies that leverage various back-scattering effects of light pulses34. However, only in recent years there have been publications demonstrating the diverse geophysical applications of low frequency DAS (LF-DAS) signals that are dominated by temperature40. In particular, Ide et al.38 found distinctive patterns with several-hours periodicity on underwater LF-DAS data from a cable offshore Japan. They proposed that these patterns were related to the thermal signature of ocean water currents and their interaction with tides and complex bathymetric features. Lindsey et al.22 had also speculated about possible internal waves (IWs) signatures on LF-DAS data collected offshore California, USA. In practice, however, the nature of the physical signatures contained in underwater LF-DAS data is not entirely understood because of the lack of ground-truth validation and in-depth description of such signals.The possibility of using Rayleigh-scattering systems to measure temperature changes had been recognized decades ago41 of the fiber sensed by DAS interrogators45. At short timescales , or between the fiber and the cable jacket and/or steel armor, are prone to cause thermal stresses on the fiber49.From a theoretical perspective, the fluctuations in both the mechanical strain and temperature fields can locally change the optical path length43. A single DFOS system acts as a dense, gauge-adjustable array of point sensors along the cable layout, and thus measures a curvilinear projection of 3D physical fields. Previous studies relied on DTS to measure different underwater environments including lake and near-coastal seafloor temperatures, some of them describing internal waves, thermal events and tidal currents56. While DTS is dedicated to absolute temperature sensing, LF-DAS could provide a significantly higher sensitivity, spatio-temporal resolution and, potentially, a considerably longer sensing range for the measurement of temperature anomalies. As we will explore latter, both instruments can be considered complementary for physical oceanography applications.The two principal Distributed Fiber Optic Sensing (DFOS) technologies alternative to DAS are Distributed Temperature Sensing (DTS) and Distributed Strain and Temperature Sensing (DSTS). As stated by their names, both techniques are naturally designed for temperature monitoring. DTS and DSTS track variations in the Raman and Brillouin back-scattered spectrum of light, respectivelyIn this study, we analyse LF-DAS  and make it manageable for signal processing in a standard workstation, we applied a temporal moving average on the strain time series of each channel independently. Then, to convert the LF-DAS apparent strain values into corresponding absolute temperature anomalies (variations), we used the approximation: 60. The deepest sensor is only a few centimeters above the seabed. The thermistor chain is located over the gently sloping shelf south of Toulon, about 4 km west of the closest cable section62  off Cap Vieux, Toulon  of Météo-France operational forecasting atmospheric model AROMEFigure entclass1pt{minimaentclass1pt{minimaentclass1pt{minimaentclass1pt{minimaentclass1pt{minima65), as attested by the AROME data 71 which is intended for decomposition of non-linear and non-stationary signals. Supplementary text The relatively short time span of the data hampers a Fourier-derived spectrogram that properly resolves LF signals in time. Furthermore, the widespread sharp patterns of the LF-DAS time series affect the reliability of the finite Fourier Transform. In order to overcome these obstacles, we conduct an Empirical Mode Decomposition (EMD) analysis75.Figure 76 spectra on continental shelf  and slope  sections where the horizontal projection of the LSPM cable is nearly linear. As expected, low-frequency signals approaching the inertial peak dominate both spectra, as illustrated by the contours. Onshore propagation components (positive apparent wavenumbers) over the continental shelf  temperature measurements independently confirmed this cooling event, which is associated with a homogenization of the water column temperature. Sea surface temperature estimates at 1.2 km-resolution provided by the operational model F2-MARS3D-MENOR120084 also confirmed this upwelling event, which started on the 27/07/2019 at the northwestern-most tip of the Gulf of Lions and propagated towards the SE, in consistency with a Mistral-wind origin  current bringing  warmer water to the area over a large portion of the water column92, which in turn could potentially be related to the multiple-day modulations present in LF-DAS, as these could produce temperature changes over several days. This highlights the potential of LF-DAS for capturing the propagation characteristics of ocean seafloor variability on multiple days time scales and suggests the study of large-scale ocean currents, which are known to account for several-days temperature fluctuations near the bottom.A cooling event corresponding to an average estimated decrease of entclass1pt{minima93 and highlight the presence of near-inertial  stresses is generally expected to be much lower than longitudinal  ones96, meaning that vertical pressure waves induced by tidal oscillations inciding a fiber in a gently sloping, flat bottom might go undetected. Furthermore, it is known that the response of DAS is generally inversely proportional to the apparent wavelengths generated by such broadside incidence angles100. On the other hand, the detection of horizontal seafloor motions induced by tides over cable sections with rugged or sloping bathymetry remains to be demonstrated for DAS.The detection of mechanical strains at tidal frequencies has only been demonstrated for DAS under laboratory conditions, although only for controlled deformations that were several orders of magnitude larger than actual tides101 is a well-known long-period strain signal that is generally expected to fade below about 2 mHz. However, it has been proposed, along with (the transient and intermittent) tectonic earthquakes, as a continuous forcing mechanism of some of the normal modes of the earth102, whose resonance frequencies partially overlap those of the several-minute period thermal variability here observed. As these normal modes could be continuously observed at the seafloor103, further analyses are required to quantify their potential contribution to LF-DAS in the form of long-period strain signals.The seismic humThe variable cross-shore extent of the shelf temperature variability of up to 4 km over time and depth can result from regional variations in the vertical thermal stratification of the ocean. Local changes in the magnitude of the thermal anomalies, reaching more than 5 K and absolute thermal rates of more than 1 K/h, might also arise from IW packets with variable amplitudes displacing the thermocline vertically. In general, shallower areas contain larger thermal anomalies than deeper regions, following the general vertical attenuation of IW away from the thermocline. These anomalies become scattered at the near-shore, as several signatures appear to accumulate and overlap, which is not surprising, as IWs are expected to degenerate considerably at the near-shore due to non-linear effects. The substantial reduction in high frequency variability over the course the 2019 experiment  against a gently sloping bottom. This would account for the “V” anomalies with slow warming and fast cooling events propagating in opposite senses . Interestingly, Lucas & Pinkel (2022) observed the same behavior at tidal frequencies, except for a reversed thermal rate asymmetry, meaning fast warming and slow cooling events. For our data, the control exerted by the direction of the slope relative to that of the anomalies ies Fig. b would s104 and the Western Mediterranean abyss73. The ubiquitous presence of near-inertial variability over the slope can be explained by the more stable ocean thermal stratification expected at these depths. Here, LF-DAS points towards persistent cold water anomalies propagating onshore, which may be of substantial relevance as these are known over the shelf10 but less so over the slope. The mean fluctuation amplitudes here are on the order of 0.01 K, while the thermal rates occasionally exceed 0.2 K/h. Assuming a vertical thermal stratification of w and h is water depth. Assuming an average slope of 0.1  is larger than 106. Both propagation vectors have equal-sign vertical components for gyroscopic IWs, that is, when 107. Taking into consideration the strong dependence of the observed IW on the continental slope bathymetry, the effect of the variable seafloor steepness and roughness has to be taken into account for a precise description of IW energy partitioning at the seafloor, including reverberations and higher order modes . However, at low frequencies, the temperature effect is expected to dominate, as evidenced by previous works and our validation in Fig. 38, related LF-DAS data acquired offshore Japan with temperature changes of a few Kelvins having apparent propagation speeds of Ide et al.109, while LF-DAS is currently restricted to absolute temperature variations because of the 44. Yet, LF-DAS offers some key advantages for monitoring thermal anomalies: over short distances  and over larger gauge lengths to achieve acceptable performances110. In contrast, the Rayleigh scattered power is 20 to 30 dB higher than the Brillouin and Raman scatterings typically used for temperature sensing, respectively111, so that longer sensing ranges are attainable with DAS (up to 100 km and more112). At the same time, diverse techniques exist to preserve optimal DAS repeatability at long distances21.Upon calibration, DSTS and DTS are capable of providing absolute temperature measurements40, it is generally expected to be a function of the composition and structure of each cable113 and its coupling and thermal insulation by the host medium, from which detailed information is often lacking. This limitation, however, could be overcome through unique, temporary or regular temperature calibrations at single or multiple cable locations with dedicated temperature sensors and/or with auxiliary DTS/DSTS systems114, depending on the required precision and possible logistics. When implemented, the SMART cable initiative115 should provide calibrated temperature sensors at the optical repeaters of new cables. It is also worth reminding the significant efforts and recent progress on the improvement of the sensing range, SNR characteristics and the simultaneous use of DAS instruments on operating telecommunication fibers120. Although standard DAS units are expected to suffer from noise increasing inversely proportional to frequency (1/f), our results show that this effect is not enough to impair the detection of the thermal oceanic signatures at the frequencies here considered. In a recent study121, the possibility to suppress the 1/f noise was demonstrated, thus opening the way for a new generation of DAS systems robust for static sensing and capable of providing absolute temperatures over periods of months or longer.The current lack of knowledge about the exact transfer function between the optical fiber response and the input ambient temperature hampers the exact estimation of the latter. Although this transfer function is reportedly linearCurrently, LF-DAS on a single cable only provides a one-dimensional view of the multi-dimensional oceanic variability, therefore more advanced wavefield processing methods  and additional constraints  could provide further insights into the 3D IW propagation parameters, such as true wavelengths, shapes and speeds. Future studies may also address other interesting physical signals and effects potentially present on LF-DAS. For instance, variable hydrostatic or hydrodynamic pressure loads and coastal surface gravity wave-related stresses could exert an effect on the thermo-optic sensitivity of the cable. Also, the degree of cable burial under sediments is expected to bias the DAS sensitivity to water temperature anomalies due to thermal insulation and potentially delay the signal response. Local turbulence that influences the thermal signatures at shorter timescales may also exist. In active volcanic regions and others with geothermic or fluid injection activity, underground heat anomalies might as well be prone to monitoring with LF-DAS.The evidence gathered in this study supports established theoretical and practical expectations on the sensitivity of DAS to ambient temperature. More specifically, we confirm previous observations of high-resolution ocean thermal signatures in LF-DAS data from an underwater fiber optic cable. Independent ocean water temperature signals recorded at sensors in the northern margin of the Mediterranean sea, separated from the cable by a couple of kilometers, correlate well in the long term with the LF-DAS signal at the nearest cable sections. Additional evidence of the good correlation between LF-DAS and temperature is independently provided by DAS and DSTS measurements along collocated fibers on the same cable. Furthermore, we highlight the presence of oceanic thermal anomalies with along-bottom extents of less than 1 km and up to 4 km (apparent wavelengths of hundreds of meters to a few kilometers) consistent with internal wave-induced oscillations of (sharp) ocean thermal gradients, having highly coherent propagation characteristics, apparent speeds clustered between 0.01 and 0.1 m/s, amplitudes ranging from 0.01 to more than 5 K, maximum absolute thermal rates of more than 1 K/h and periods ranging from tens of minutes and up to about the inertial period of the study region (17.5 h). The behavior of these thermal oscillations varies across the continental shelf and slope sections of the cable, pointing towards two markedly different internal wave regimes. Stable, near-inertial oscillations dominate the continental slope, while thermal stratification oscillations are evident along the shelf that are modulated on several-day scales. The clear presence of an upwelling event lasting several days on the same data, and inducing a water temperature decrease of at least 2 Kelvin at the seafloor also highlights the potential of LF-DAS for long-term underwater temperature studies.128. DAS can be optimally generalized for these various applications, while at the same time it can provide densely sampled temperature signals across the ocean without the need for offshore campaigns, as shown in this study. With DAS measurements we may describe internal waves more systematically, i.e. their occurrence, characteristics, and better describe several aspects of their lifecycles . This could be leveraged to test the performance of numerical models either explicitly reproducing these processes or those at lower resolution attempting to parameterize them. This provides new experimental opportunities for oceanographic and hydrographic applications using existing telecommunications cables and other optical fiber infrastructures which, additionally to the phenomena considered in this study, could potentially be useful to study e.g. bottom temperature variability at various temporal and spatial scales (which is key for turbulence parameterizations), marine heatwaves, geothermal heat transfer across the seafloor and the response of marine ecosystems to thermal anomalies, e.g. benthic environment monitoring via combined temperature and biological (underwater acoustic) observations.In recent years, seismological and acoustical instrumentation has been implemented to study ocean phenomena58. The time series data sampling frequency was 100 Hz in the first couple of days of the campaign and then switched to 500 Hz.The DAS interrogator unit used for our main analysis is a 100.The DSTS system used to validate the simultaneous LF-DAS (indirect) measurements was a Febus Optics G1-C set to record with a gauge length of 10 m and sampling resolution of 2.0 m over 30 km. The temporal sampling was set to 15 min to keep the data noise level at a reasonable level. The DAS system in this case was a Febus A1-R DAS interrogator with gauge length of 10 m and sampling resolution of 4.8 m over 40 km of cable. For details on the experimental setting of the LSPM cable, the reader is referred to Lior et al.The thermistor chain used for the study is composed of a moored line equiped with a deadweight and a series of Nokalon floats, having an array of temperature sensors (HOBO Water Temp Pro v2) attached to the line. The mooring line consists of a base serving as ballast (weight of approximately 450 kg) and three ropes supported by the floats: two outer ropes forming the frame of the system and a central line supporting the temperature sensors  sections during acquisition due to two separate interrogator reboots. Visual inspection of the raw data shows that each of these sections has noticeable value offsets and two time gaps in-between (4 and 76 minutes each) in between , the apparent strain differences measured by DAS are expected to be caused by refractive index variations of the fiber due to temperature changes in the environment, instead of being caused by LF strain-related elongations on the fiber. Based on the phase variations induced by changes in the optical path length For the comparison of LF-DAS with the thermistor chain in Fig. Pearson correlation coefficient of the multiple-day variability was found by comparison of the time series of the preprocessed LF-DAS converted to temperature changes (without filtering) with the up-sampled thermistor chain temperature signal at 50 m depth, which has a lower sampling rate. 23 consecutive channels  have Pearson correlation coefficients at or above 0.8. For the multiple-hour variability, the long-term trend of each time series was found via uniform convolution moving-average and then removed from each, so to only compare the fast variability of both. The number of samples of the uniform convolution filter was selected as the one that maximized the Pearson correlation coefficient of the fast variability signal, and was found to be equivalent to almost one day of data.Supplementary Information.Supplementary Video 1.


Intravascular cutaneous anaplastic large cell lymphoma (ALCL) is an extremely rare non-Hodgkin lymphoma that proliferates in the lumen of small blood vessels and has a propensity to manifest in the skin. Most reported cases of intravascular lymphoma described in the literature are of large B-cell lymphomas, making T-cell lymphomas incredibly rare. As such, we present the case of an 87-year-old male with primary cutaneous intravascular anaplastic large T-cell lymphoma that initially presented with an erythematous, subcutaneous nodule on the right mid-abdomen. We report the immunohistochemical results showing lymphoma cells staining positively for CD3 and CD30 and lacking expression of anaplastic lymphoma kinase, pan-cytokeratin, CD10, CD20, and SOX10. We also review and compare previously reported cases of intravascular ALCL with primary cutaneous involvement. Cutaneous-anaplastic large cell lymphoma (C-ALCL) is a CD30-positive T-cell lymphoma within the subset of primary cutaneous CD30+ lymphoproliferative disorders with proposed criteria for diagnosis to include large, anaplastic, pleomorphic cells with a predominance of CD-30+ cells (>75%) and the absence of clinical evidence of mycosis fungoides . PrimaryAn 87-year-old male with a medical history of follicular non-Hodgkin lymphoma, treated over 10 years prior, presented to the clinic with a firm, erythematous, subcutaneous nodule on the right mid-abdomen (Figure A review of the systems was negative. Initially, the clinical suspicion was that of an epidermal inclusion cyst. A small elliptical excision of the nodule was performed, and histopathology results revealed a superficial scant perivascular infiltrate of lymphocytes with an infiltrate of larger atypical cells in the deep dermis, which were confined to the vascular spaces Figure . The larLater, an erythematous patch adjacent to the prior subcutaneous nodule was noted at the time of suture removal. There was clinical suspicion of this new patch for another lymphoma. A 5-mm punch biopsy was performed, revealing an identical histopathologic diagnosis and immunohistochemistry findings as the first nodule. The second biopsy revealed multiple dilated ectatic vascular spaces containing large pleomorphic mononuclear cells within the dermis that were surrounded by a relatively bland-appearing lymphocytic inflammatory infiltrate. CD3 and CD30 were positive in the cells within the intravascular spaces. CD31 highlighted the cells were confined to the vascular spaces Figure . ALK staIntravascular lymphoma is a rare form of lymphoma characterized by large, malignant cells within the lumen of the vasculature. Currently, the WHO classification system only identifies B-cell intravascular lymphoma as a distinct entity . As suchNguyen et al. , MetcalfIn summary, intravascular C-ALCL is an infrequent diagnosis. The prognosis is unclear whether this lymphoma behaves more aggressively, similar to other intravascular lymphomas, or behaves similarly to primary cutaneous CD-30-positive ALCL. Distinction from systemic ALK-negative ALCL is essential as the prognosis is unfavorable in systemic ALK-negative ALCL, and an appropriate staging workup is necessary to distinguish the two. Existing cases give us a glimpse into potential treatment options for the inflicted patients, but the efficacy of treatment and data on remission are limited. This uncertainty highlights the need to investigate additional cases to determine the appropriate treatment and clinical management of these patients.


BackgroundRhino orbital mucormycosis is a rare and very aggressive entity. A sudden rise of this entity has been noticed with the insurgence of the COVID-19 pandemic both among immunocompromised and immuno-competent patients. This study was done to determine any possible correlation between these two deadly diseases.Materials and MethodsThis was a retrospective observational study done in the pathology department of a tertiary care center in North India over a three-year period (January 2019 - December 2021). Patient details along with relevant clinical data were retrieved from the patient’s record file. Hematoxylin and eosin-stained slides of diagnosed cases were taken from the department records.ResultsA total of 45 patients  were included in the study, seven of which were ophthalmic exenteration specimens. The mean age of the patients was 52.68 years. Fifteen cases showed COVID-19 reverse transcription-polymerase chain reaction (RT-PCR) positivity. Histopathology revealed the presence of mucormycosis in all the cases. There were six cases showing granuloma formation and 14 cases revealed mixed fungal infection. Optic nerve involvement was seen in six cases of exenteration specimens.ConclusionsThe present study showed a sudden resurgence of secondary fungal infections, especially during the second wave of the COVID-19 pandemic. Associated co-morbid conditions and injudicious use of steroids and antibiotics have been the cause of depressed immunity leading to the infections. One must be aware of such co-infections to facilitate timely medical management to reduce morbidity and mortality. Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) declared a pandemic worldwide, has presented a formidable medical challenge to the health system since 2020. Infection with CoV-2 predominantly affects the respiratory system with variable severity ranging from a common cold to more severe diseases including pneumonia . The relThis was a retrospective observational study done in the Department of Histopathology in a tertiary care center in North India over a three-year period (January 2019- December 2021). A total of 45 proven cases of mucormycosis in both rhino-nasal biopsies, as well as ophthalmic exenteration specimens subjected to histopathological examination, were included in the study. This did not include the six cases seen in the pre-COVID era. Demographic and clinical detail documented in the patient (45 cases) record files along with detail of grossing of the specimen from the departmental records were noted as per the protocol pro-forma.Routine laboratory investigations like complete blood count, random blood sugar, renal function test, D-dimer, and glycated hemoglobin (HBA1c) wherever available were noted down. Magnetic resonance imaging of the orbit and brain did in most of the ophthalmic exenteration specimens to assess the extent of the disease and the findings were retrieved from the patient's record file.Smaller biopsies were measured and processed as per the laboratory protocol. Each of the ophthalmic exenteration specimens was measured and examined for any areas of necrosis or hemorrhage in the peri-orbital soft tissue. The optic nerve was identified and the resection margin was sampled and processed separately in all the cases. An anteroposterior sagittal section through the specimen was made with the identification of internal structures. Any abnormality if present was noted. The sections taken were processed as per the laboratory protocol.Hematoxylin and eosin (H&E) stained slides along with blocks and special stain slides like Grocott-Gomori methenamine silver (GMS), and if available, periodic acid Schiff (PAS) of all the cases were retrieved from the histopathology records and reviewed to see pathological changes caused by fungus. The diagnosis of mucormycosis in sino-orbital specimens was based on the demonstration of broad septate hyphae with right angle branching on histopathological and/or 20% potassium hydroxide (KOH) preparation as well as Sabouraud's dextrose agar culture reports . In caseStatistical analysisThis was an observational descriptive study with the use of counts and percentages. The data was plotted on the MS Excel sheet with all the analyses performed on SPSS .Clinicopathological evaluation of a total of 45 cases (excluding pre-COVID era cases) of sino-orbital fungal infections reported on tissue biopsies (38 cases) and ophthalmic exenteration (seven cases) was done during the study period. Ophthalmic exenteration cases were encountered only during the second wave of COVID-19. A rise in these infections was seen in the present study with only six cases (13.3%) reported in the year 2019 (pre-COVID era) which rose to 14 (31.1%) during the first wave of the COVID-19 pandemic (2020) and to 31 (68.8%) in the second wave (2021).Demographic profileThe majority of the patients in our study were males (34 cases) with male to female ratio of 3:1. The age group of the patients ranged from 23-70 years (mean age 52.68 years). Most of the patients (83.7%) presented solely with nasal cavity or paranasal sinus involvement with seven cases exhibiting maxillary and orbital involvement also. Clinical presentation and risk factors.Duration of clinical symptoms ranged from two days to three months with late presentation seen among patients having ocular involvement.Nasal stuffiness, blockage, a nasal mass, and discharge were the common clinical presentations of our patients. In addition to this, patients having orbital involvement (seven cases) showed periorbital pain, swelling, congestion, watering of the eye, and restricted ocular movement along with a diminution of vision. Fundus examination in these cases revealed features of optic disc edema and central retinal artery occlusion (CRAO) in four cases.Relevant history for co-morbid conditions was seen in 55.5% (25/45 cases) of the patients. Most of whom  were on anti-hyperglycemic treatment. Six of these patients in addition were on antihypertensives also.Laboratory investigationsCOVID-19 testing report could be retrieved only from 27 cases from the record file, of which 15 cases (33.33 %) showed positive results on RT-PCR (Reverse transcriptase- polymerase chain reaction) testing. Five cases in 2020 and seven cases till June 2021 tested negative on admission. Repeat testing was not done in any of these cases.Hematological and relevant biochemical parameters were available in just a few of the patients Table , most ofThe majority of the laboratory parameters were deranged in patients who underwent ophthalmic exenteration. The details have been mentioned in Table Radiological findings could be retrieved in 5/7 patients who underwent ophthalmic exenteration. The findings were almost common to all and showed involvement of nasal and orbit-o-maxillary areas with a soft swelling in intra-orbital tissues, proptosis, and necrosis to various extents. Secondarily, brain involvement occurred in 3/7 cases who also developed cerebro vascular accident (CVA). Cavernous sinus thrombosis (CVT) occurred in 1/7 of patients.Gross and microscopic findings were noted from the department records in all 45 cases and the slides retrieved were reviewed by the authors. Gross specimens were mostly either excision biopsies or functional endoscopic sinus surgery (FESS) curetting. Ophthalmic exenteration specimens were received in seven cases Figure . MaxilleThe optic nerve was involved in the infective process and showed the presence of mucormycosis in six of the seven (85.1%) ophthalmic exenteration specimens Figure . HistopaThe patients in this study were started on intravenous anti-fungal treatment (amphotericin B) and were discharged in satisfactory condition.COVID-19 has emerged as a global pandemic. Extensive and injudicious use of antibiotics, steroids, and comorbidities has developed a more worrisome feature of this pandemic in form of superimposed fungal infections, especially during the second wave , 5. The The present study was done based on the observation regarding the remarkable increase in rhino-orbital mucormycosis in routine biopsies during the COVID-19 pandemic as compared to the previous year's findings (six cases only in 2019). Even though many studies have been published since the pandemic, most of them are either reported as case studies/series or as literature reviews. However, there aren’t many regarding the spectrum of fungal infections in a rural tertiary care center set up in North India, hence, an effort was made to compile the data depicting the same. The demographic profile showed a majority of the patients in our study to be males with their ages ranging from 23-70 years which was in accordance with various other studies -13.All the patients in our study gave a brief history of mild to moderate symptoms pertaining to COVID-19 infection. Non-specific symptoms like nasal stuffiness, blockage, facial swelling, a nasal mass, and discharge were seen in most of the patients as observed in other studies , 8, 10. Orbital infections are extremely rare and usually develop from the infected adjacent paranasal sinuses or through direct traumatic inoculation into the orbit , 24-25. The time duration between the occurrence of COVID-19-related manifestations and the development of rhino-orbital fungal infection in various studies ranged from three to 42 days , 15, 17.Details regarding COVID-19 testing were documented in only 27 cases of which only 15 33.33 %) showed positive results on reverse transcription-polymerase chain reaction (RT-PCR) testing. This was discordant with a majority of the studies, whereby almost all the patients with associated mucormycosis showed COVID-19 positivity [3.33 % shThe majority of the previous and recent studies in the literature reflected immune-compromised status or comorbid conditions like diabetes mellitus (DM), chronic hypertension, and kidney diseases to be predominantly responsible for the development of fungal diseases ,-15, 17.Among the other cofactors contributing to rhino-orbital fungal infections, steroid intake and injudicious use of antibiotics have been mentioned in various studies -8. No da.Contaminated oxygen was considered a source causing fungal infections. However, none of our patients required mechanical ventilation or any kind of oxygen support which was also supported by a few studies which also showed the same , 17, 22.Similar to a few studies, no history of any comorbid condition was seen in the rest of the 18 patients in our study. This diverts our attention to other unknown factors which can be responsible for fungal co-infections , 16.. Medical records regarding the same were available in only a few cases, the majority of which showed deranged parameters, which were in concordance with the above-mentioned studies. The reason for the non-availability of the laboratory findings could be attributed to a few reasons according to the authors, the most common being non-documentation of the laboratory results due to extensive workload. The other reason could be, that the rhino-nasal biopsy was more of an out-patient procedure with patients not requiring stringent pre-operative investigations whereas patients who had ophthalmic involvement required major surgery and hence the detailed investigations.Deranged hematological and biochemical laboratory findings in the form of anemia, neutrophilia, lymphopenia, raised postprandial blood sugar (PPBS), HbA1c, serum creatinine, c-reactive protein (CRP), pro-calcitonin, D-Dimer, and IL-6 has been associated with COVID-19 disease , 17, 19.CT scan of PNS was done in five ophthalmic exenteration cases only. It showed nasal and orbito-maxillary involvement with swelling in intra-orbital tissues, along with necrosis which was compatible with other studies , 28.Microscopic examination of both FESS and ophthalmic exenteration showed infiltration by mucormycosis species in a majority 31/45) of the cases. Similar findings were seen in most of the studies -13, 15. /45 of thRhino-orbital mucormycosis (ROM) can be non-invasive (mycetoma) or invasive with the latter exhibiting acute and chronic (granulomatous and non-granulomatous) forms. More than half of our cases (55.5%) were the invasive type with granulomatous pathology seen in six cases. The present study showed a variable amount of tissue necrosis (66.6%) on histopathology which contained the maximum density of fungal organisms. Similar findings were also observed in other studies , 20, 25.Tissue for KOH mount and fungal culture could be retrieved in only 14 cases, seven of which confirmed the histological diagnosis of mucormycosis. The negative yield on KOH mount/ culture is assumed to be due to the aggressive processing of the specimen before the plating medium. Similar findings have also been documented by a few other authors , 29-30.LimitationsThis was more of an observational single-center study in a rural setup with a smaller number of cases. Relevant and mandatory clinical and laboratory data required for the study were also missing in some of the patient's medical records. From the author's point of view, the probable reason for missing data could be increased workload which might have led to the non-entry of the relevant data in the medical record files.Upsurge in rhino-orbital fungal infections has been seen among COVID-19 patients and is commonly attributed to immune dysregulation. Injudicious use of antibiotics/ steroids and with no treatment protocol in place due to the virus being novel, along with associated co morbid conditions (DM and HT) added to crisis. Histopathology plays a very important role with regards to aiding in early diagnosis and hence prompt and appropriate treatment of the fungal infections as seen in our study.An interesting thing which was also noted in our study was that about one third of the patients did not have decreased immunity which attracts our attention to think and search about other parameters which can be the causative factors for these co-infections in Indian scenario. A large-scale multi-centric study would help to gain useful data on this deadly disease so as to combat secondary infections.


However, many individuals still do not respond to or are intolerant of these therapeutic changes. For the most difficult-to-treat patients, commonly referred to as having refractory depression, electroconvulsive therapy (ECT) and repetitive transcranial magnetic stimulation (rTMS) can be used. However, ECT and rTMS have major clinical or logistical constraints that make long-term use difficult. In view of these therapeutic challenges, new treatment options are needed.7 Although concerns remain about its long-term safety and potential for abuse or diversion, the off-label use of ketamine for the treatment of patients with TRD has been expanding in the United States.8 While ketamine is a racemic mixture of 2 stereoisomers, the S-enantiomer esketamine  was approved by the U.S. Food and Drug Administration on March 8, 2019, as a nasal inhalation treatment for adults with TRD.A potential new therapeutic target is the N-methyl-D-aspartate (NMDA) receptor. Case reports and several small clinical trials have found that ketamine, an intravenously administered anesthetic agent that binds to the NMDA receptor, can rapidly improve depression symptoms in some patients with TRD.https://icer-review.org/material/trd-final-evidence-report-and-meeting-summary/.The Institute for Clinical and Economic Review (ICER) performed a systematic literature review and cost-effectiveness analysis to evaluate the health and economic outcomes of esketamine for the treatment of TRD. Complete details of ICER’s systematic literature search and protocol, as well as the methodology and model structure for the economic evaluation, are available on ICER’s website. In this article, we present the summary of our findings and highlights of the policy discussion with key stakeholders regarding the overall value of esketamine that took place at a public meeting of the Midwest Comparative Effectiveness Public Advisory Council on May 23, 2019. The detailed report is available on the ICER website at 11 2 of which were conducted in patients aged 18-65 years (TRANSFORM-1 and -2),10 while the third was conducted in patients aged 65 years and older (TRANSFORM-3).11 Patients in all 3 trials were randomized to receive either esketamine or placebo nasal spray twice weekly, each combined with 1 antidepressant that patients had not used during the current depressive episode (background anti-depressant). The primary measure of clinical benefit assessed in the 4-week RCTs was change in depressive symptoms using the Montgomery–Åsberg Depression Rating Scale (MADRS). Clinical response, defined as 50% or higher reductions in MADRS scores, and remission, defined as a MADRS score of 12 or less, were also assessed. At baseline, 36%-40% of patients in the RCTs had failed 4 or more antidepressants; average duration of current episode ranged from approximately 2 to 4 years; and, on average, patients had severe depression (MADRS mean ≥ 35). In addition to the short-term RCTs, we also evaluated 1 phase 3 maintenance study of esketamine designed to primarily assess relapse prevention (SUSTAIN 1) and a 48-week open-label trial designed to assess long-term safety of esketamine.We identified 3 similar 4-week randomized controlled trials (RCTs) of esketamine,P = 0.01).9 However, a statistically significant difference was not observed between esketamine and placebo in TRANSFORM-1 and TRANSFORM-3.11 We conducted a random effects meta-analysis of the 2 RCTs that were homogenous in patient population (TRANSFORM-1 and -2), and the result favored esketamine, showing a greater improvement on MADRS score for esketamine plus background AD compared with placebo plus background AD . On the secondary outcomes, results of the meta-analysis showed that patients on esketamine plus background AD were more likely to achieve clinical response compared with placebo plus background AD , while the relative risk of clinical remission was also superior but was not statistically significant . In the relapse prevention study (SUSTAIN 1), maintenance esketamine plus background AD decreased the risk of relapse by 51% among stable remitters .12Esketamine plus background antidepressant (AD) demonstrated statistically significant improvement in MADRS score relative to placebo plus a background AD at 4 weeks in TRANSFORM-2  program in order to monitor its abuse potential. Finally, MDD patients with psychotic features or other coexisting psychiatric conditions were excluded, thus, limiting the generalizability of the findings.We evaluated the cost-effectiveness of esketamine plus background AD compared with background AD alone in patients with TRD using a de novo decision analytic model from a U.S. health care sector perspective. The base-case Markov model was developed with 3-month cycles and ran over a lifetime horizon. The baseline characteristics of the modeled cohort reflected the weighted average across the 2 RCTs of esketamine conducted in patients aged 18-65 years (TRANSFORM-1 and -2), with a mean age of 46.0 years and a mean MADRS score of 37.4.13Patients entered the model receiving esketamine plus background AD or background AD alone and could either have an effective , partially effective , or insufficient response to treatment. Patients were treated with up to 3 alternative oral ADs if they had an insufficient response to treatment. Clinical inputs regarding the efficacy of esketamine plus background AD and background AD alone were derived from the meta-analysis of the key trials of esketamine (TRANSFORM-1 and -2), while the efficacy of alternative oral ADs were derived from the STAR*D trial, a pragmatic study evaluating numerous treatments for depression.Results from our base-case cost-effectiveness analysis showed that compared with background AD alone, esketamine plus background AD had incremental cost-effectiveness ratios of approximately $198,000 per quality-adjusted life-year (QALY) gained and approximately $2.6 million per life-year (LY) gained, which exceeds the commonly accepted cost-effectiveness threshold range of $100,000-$150,000 per QALY gained or per LY gained .Our analysis was limited to the cost-effectiveness of esketamine plus background AD versus background AD alone due to the lack of comparative effectiveness data on esketamine compared with other commonly used treatments of TRD. In addition, we had very limited data on how the number of treatments failed during a person’s lifetime, pattern and frequency of depression episodes, and how severity of the episodes affected treatment effectiveness and cost of care.The Midwest Comparative Effectiveness Public Advisory Council (Midwest CEPAC) is one of the independent appraisal committees convened by ICER to engage in the public deliberation of the evidence on clinical and cost-effectiveness of health care interventions. The Midwest CEPAC is composed of medical evidence experts, including practicing clinicians, methodologists, and leaders in patient engagement and advocacy. Their deliberation includes input from clinical experts and patient representatives specific to the condition under review, as well as formal comment from manufacturers and the public. A policy roundtable concludes each meeting during which representatives from insurers and manufacturers join clinical experts and patient representatives to discuss how best to apply the findings of the evidence to clinical practice, insurance coverage, and pricing negotiations.The ICER report on esketamine was the subject of a Midwest CEPAC meeting in May 2019. Following discussion, the CEPAC panel members voted 14-3 that the evidence was adequate to demonstrate the superiority of esketamine plus background AD versus background AD alone. The CEPAC panel also voted on “other potential benefits” and “contextual considerations” as part of a process intended to signal to policymakers whether there are important considerations when making judgments about long-term value for money not adequately captured in analyses of clinical and/or cost-effectiveness. The results of these votes are shown in 14 questions on long-term value for money are subject to a value vote when incremental cost-effectiveness ratios for the interventions of interest are between $50,000 and $150,000 per QALY in the primary “base case” analysis. As previously described, the estimate of $198,000 per QALY exceeds the higher end of this range, thus, esketamine was deemed “low value” without a vote of the panel.As described in ICER’s recent value assessment framework,https://icer-review.org/material/trd-final-evidence-report-and-meeting-summary/. However, the key policy recommendations are as follows:The policy roundtable discussion explored how best to translate the evidence and broader perspectives discussed into clinical practice and into pricing and insurance coverage policies. The full set of policy recommendations can be found in the final evidence report on the ICER website at Manufacturers and researchers should conduct studies directly comparing esketamine and other treatment options using standardized research protocols and outcomes that reflect what matters most to patients; this would allow real-world, long-term assessment of comparative effectiveness.Patient eligibility:Diagnosis: Adult patients with TRD defined as having tried 2 or 3 medications from 2 or more drug classes in the current episode with inadequate response or intolerance.Exclusion: Due to concerns about abuse and misuse, patients with active substance use disorders may be excluded from consideration for esketamine, but criteria should not be so stringent as to exclude patients with TRD and a history of substance use who may benefit from esketamine when used as directed.Step therapy: For patients meeting the criteria previously suggested, the addition of step therapy through treatments such as ECT, rTMS, and antipsychotics were not recommended due to uncertainty about relative risks, benefits, and logistical constraints compared with esketamine.Potential provider criteria: Esketamine may be covered only if prescribed by, or in consultation with, a specialist clinician with formal training in psychiatryGiven the considerable uncertainty that remains regarding the longer-term benefits and risks of esketamine, it is reasonable for insurers and other payers to develop prior authorization criteria to ensure that patients are carefully selected and managed by clinicians with the necessary expertise to ensure appropriate care. Considerations for prior authorization include:Payers should develop mechanisms to adequately compensate clinicians for the expenses associated with monitoring and delivering esketamine within the specification of the REMS program.Current evidence demonstrates short-term clinical benefit of esketamine versus placebo. However, concerns remain about its safety with long-term use. Furthermore, at current pricing in the U.S. market, the incremental cost-effectiveness ratio for esketamine is above the commonly cited cost-effectiveness thresholds and thus was judged to represent low long-term value for money. Further research is needed to evaluate whether there are subgroups of patients that can be identified who are most likely to benefit from esketamine in the short term. Further research is also needed to evaluate the outcomes of esketamine use beyond the very short duration of existing trial data. Having a new treatment for TRD is important given significant unmet clinical need, but evidence about the relative benefits and risks of esketamine compared with other treatments remains quite limited.


Research examining online health communities suggests that individuals affected by chronic health conditions can obtain valuable information and social support through participation in peer-to-peer web-based information exchanges, including information sharing and seeking behaviors. The risks and rewards of these same behaviors in the case of acute illnesses, such as COVID-19, are less well understood, though there is reason to believe that individuals with COVID-19 and other acute illnesses may accrue similar benefits.This study examines the propensity of American adults to disclose and discuss their COVID-19 diagnosis and symptoms on social media while actively infected with the SARS-CoV-2 virus, as well as to engage in peer-to-peer information seeking in order to better understand the illness that they are experiencing. Additionally, this study seeks to identify the motivations for these behaviors as well as their subsequent impacts on perceived social connectedness and health anxiety in patients with COVID-19.We conducted a representative survey of 2500 US-based adults using a sample purchased through an industry-leading market research provider. Participants were selected through a stratified quota sampling approach to ensure a representative sample of the US population. Balanced quotas were determined (by region of the country) for gender, age, race, ethnicity, and political affiliation. Responses were analyzed from 946 participants who reported having an active social media account and testing positive for COVID-19 at least once since the start of the pandemic.The results show that only a small portion of social media users  chose to disclose and discuss their COVID-19 diagnosis while infected with the virus. However, among those who did, an overwhelming majority  said that doing so helped them feel more connected and supported while infected with the virus. A larger percentage of the 946 respondents  engaged in peer-to-peer information seeking while infected with COVID-19. Among those who did, a large majority  said that doing so was “helpful,” but more than one-third  said that reading about other people’s experiences made them “more worried” about having COVID-19, while 33% (108/319) said that it made them “less worried.” Illness severity and political affiliation were significant predictors of both information sharing and seeking.The findings suggest that the benefits (and risks) associated with online health communities are germane to patients with acute illnesses such as COVID-19. It is recommended that public health officials and health care providers take a proactive approach to cultivating professionally moderated forums supporting peer-to-peer engagement during future outbreaks of COVID-19 and other acute illnesses in order to improve patient outcomes and promote social support and connectedness among infected patients. In September 2020, the World Health Organization (WHO) noted that the COVID-19 pandemic has been the first public health crisis in history “...in which technology and social media are being used on a massive scale to keep people safe, informed, productive and connected” , and EurAmong other considerations, this growing body of research has examined the extent to which information consumers have used social media for pandemic-related news and updates ,5, as weWhile several researchers have found evidence of elevated health anxiety among SNS users during the COVID-19 pandemic -10, prevWith this in mind, we conducted a survey of 2500 American adults in order to better understand the propensity of SNS users to share and discuss their personal COVID-19 diagnoses on social media, as well as to engage in peer-to-peer information seeking while actively having a SARS-CoV-2 infection. From this sample, which included 946 SNS users who had tested positive for COVID-19, we examined (1) the factors associated with personal information seeking and sharing behaviors, (2) whether COVID-19–infected individuals shared personal or medically oriented information, and (3) the subsequent impacts of these behaviors on the individual’s sense of connectedness and health anxiety. This study seeks to help both individual SNS users and health professionals better understand the risks and rewards associated with web-based information sharing and seeking during periods of acute illness, as well as to extend our existing knowledge about online health communities to this same context.While this research does not examine a specific online health community, the rationale for this study can be found in the literature surrounding online health communities and their perceived benefits. Online health communities refer to digital spaces that allow for the formation of communities of exchange among geographically dispersed individuals with shared health conditions . Within Importantly, participation in online health communities extends beyond patients with health conditions to include dedicated caregivers and concerned family members and friends. Within these online health communities, participants engage in behaviors such as (1) information seeking and learning, (2) information sharing and disclosure, and (3) community building ,16,19,22Despite the numerous benefits associated with online health communities participation is not without its potential downsides. Along with the personal privacy risks associated with sharing diagnoses on the web , researcWhile previous studies have focused primarily on participation in online health communities among patients with chronic health conditions, there are reasons to believe that these same benefits (and risks) may accrue to patients with acute, short-term illnesses (such as COVID-19). In particular, the COVID-19 pandemic has led to significant increases in health anxiety, due in large part to the uncertainty and ambiguity surrounding issues of transmission, testing, treatment, and vaccine efficacy over the past 3 years -10. ThisSeveral recent studies have considered social media usage related to the COVID-19 pandemic, including the propensity of SNS platforms to facilitate the spread of misinformation ,36, the This study adds to this literature by considering how these behaviors affect the experiences of patients with COVID-19. In conducting this exploratory study, we considered the following research questions:Research question 1: How likely are SNS users to share their diagnosis on social media while infected with COVID-19?Research question 2: What types of information do SNS users share about their COVID-19 experience?Research question 3: For what reasons do SNS users choose to share their COVID-19 experiences on social media?Research question 4: Is COVID-19 diagnosis sharing on social media correlated with feelings of greater social support and connectedness?Research question 5: How likely are SNS users to engage in peer-to-peer information seeking on social media when diagnosed with COVID-19?Research question 6: How is peer-to-peer information seeking related to health anxiety among SNS users with COVID-19?Understanding these patterns of behavior, as well as how they correlate with patient outcomes such as social connectedness and health anxiety, may help public health officials and health care providers to better leverage emerging technologies and engage with patients and the public in a more deliberate and targeted manner, particularly in digital spaces. In the long term, this could include improved professional facilitation of (and intervention in) online health communities, which may aid in combating the spread of digital misinformation. As demonstrated in previous research, tracking and analysis of web-based diagnosis sharing may also allow health professionals to better understand patient experiences, including the symptomology of rapidly spreading acute illnesses such as COVID-19 -41. ThisThe initial sample for this study included a survey of 2500 US-based adults, which was conducted between February 27 and March 9, 2023. The survey was fielded through Prodege, an industry-leading market research provider, and sponsored by the University of South Florida’s internal Interdisciplinary Research Grant Program. Survey respondents were selected through a stratified quota sampling technique to ensure that the sample was representative based on gender, age, race, ethnicity, education, and political affiliation . Demographic quotas were determined based on data from the US Census Bureau’s 2019 “American Community Survey” , and polFrom this initial sample of 2500 respondents, the current analysis focuses only on those respondents who have an active personal account on at least one social media platform and have tested positive for COVID-19 at least once since the start of the pandemic (N=946). Respondents who have tested positive for COVID-19 more than once during the course of the pandemic were asked to think about their first confirmed COVID-19 diagnosis. Responses to the survey were analyzed using descriptive statistical techniques, and 2 logistic regression models were fitted in order to better understand the factors associated with individual SNS users’ propensity to engage in peer-to-peer information sharing and seeking while infected with COVID-19. The findings from this analysis are presented below.This study was submitted to the University of South Florida’s institutional review board (IRB) for review and approval (STUDY #005318). The IRB determined that the study met the criteria for exemption from IRB review  and classified the study as “nonhuman subjects research.” This designation arises from the fact that the survey is fielded through a third-party panel vendor, and the research team does not interact directly with respondents or participants. Furthermore, no personally identifying information is collected by or transferred to the researchers. While the third-party panel vendor collects these data, only deidentified secondary data are transmitted to the researchers. Given this designation, a modified or shortened informed consent protocol was used, wherein respondents were provided a summary of the study and accompanying risks, with their choice to proceed with the survey being registered as consent.The survey responses show that just over a quarter  of active SNS users who have tested positive for COVID-19 chose to share their diagnosis on social media. Among this group of respondents, 9% (85/946) waited until the illness had passed to discuss their experience on the web, and 18% (166/946) discussed having COVID-19 while actively infected with the virus . AdditioWhile only 1 in 4 SNS users opted to discuss their COVID-19 diagnosis on social media, those who did overwhelmingly agreed that doing so helped them feel more connected and supported when dealing with the illness. In total, 82% (206/251) said that sharing their diagnosis helped them feel more connected and supported, with 47% (118/251) saying that it helped “a great deal,” while 35% (88/251) said that it helped “a little.”Respondents’ stated reasons for sharing their COVID-19 diagnosis on social media showed a mix of personal and altruistic or empathetic motivations. The most common reason for sharing or disclosure was to “update friends and family members on my well-being” . Other personal reasons for disclosure included “to feel less isolated” , “for moral and spiritual support” , and “to vent or complain about COVID-19” .Many SNS users also reported sharing their diagnosis for altruistic reasons . For example, nearly half  said that they disclosed their diagnosis in order to “help others know what to expect from COVID-19,” while 27% (69/251) did so to “encourage others to get tested and follow public health guidelines.” Around 25% (63/251) said that they shared their diagnosis in order to “tell others that COVID-19 was serious,” and 9% shared “to tell others that COVID-19 was not that bad.”Building on these descriptive summaries, we fitted a logistic regression model in order to identify and better understand the factors associated with diagnosis disclosure among SNS users. The results are reported in P<.001). Even those with a severe case of COVID-19 that did not require hospitalization were over three times  more likely to do the same (P=.02). P=.06, ceteris paribus. This rose to P=.16 among those with a severe case of COVID-19 and to P=.38 among those whose COVID-19 required hospitalization.  than those who did not rely on social media at all.  used social media to learn more about what others had experienced when infected with the virus . Those wWhile respondents overwhelmingly said that it was helpful to use social media for peer-to-peer information seeking after testing positive for COVID-19, responses were divided when it came to the psychological impacts of this behavior. For example, 36% (115/319) of those who used social media for peer-to-peer information seeking said that doing so made them “more worried” about having COVID-19, while 34% (108/319) said that it made them feel “less worried.” Just under a third  said that peer-to-peer information seeking did not affect how worried they were about having COVID-19.P=.06). Democratic respondents were more likely than all others to engage in peer-to-peer information seeking, but this difference was only statistically significant in the case of Republicans. Republican voters were nearly two times less likely to engage in peer-to-peer information seeking than Democrats .An additional logistic regression model was fitted to better understand the antecedents of peer-to-peer information seeking on social media . The resP=.07, ceteris paribus. This rose to P=.47 for those who relied on social media “a little” for COVID-19 information and to P=.58 for those who relied “a great deal” on social media.Unsurprisingly, reliance on social media for COVID-19 information was consistently and positively related to the likelihood of engaging in peer-to-peer information seeking. Standard demographics, including gender, age, race or ethnicity, and education, were not significant predictors of either information seeking or diagnosis disclosure.Throughout the COVID-19 pandemic, SNS such as Facebook and Twitter have played a formidable role in helping users stay informed and connected -4. In thPrevious research suggests that participation in online health communities can help those affected by chronic health conditions gain valuable medical information and experience lower levels of perceived social exclusion and improved psychological well-being ,15,21,22While these benefits are significant and warrant further consideration, it is also notable that peer-to-peer information seeking can have a pernicious effect on health anxiety for some SNS users. In this study, we found that 36% 115/319) of those who engaged in peer-to-peer information seeking when infected with the SARS-CoV-2 virus said that doing so led them to be “more worried” about having COVID-19. This is consistent with findings from several studies that have demonstrated a link between web-based information seeking and health anxiety ,29, incl of thoseAnother area of concern that emerged in the current findings was the sizeable relationship between political affiliation and the propensity of SNS users to engage in peer-to-peer information seeking and sharing. Specifically, self-identified Democrats were 2 times more likely than Republicans and political Independents to engage in web-based diagnosis sharing and 1.9 times more likely than Republicans to engage in peer-to-peer information seeking. On one hand, this relationship is unsurprising, as data have consistently shown high levels of COVID-19 politicization throughout the pandemic, particularly in the US context ,48. HoweOver the past 3 years, significant attention has been paid to web-based behavior (including information seeking and sharing) during and related to the COVID-19 pandemic. While these studies have yielded valuable insights into the growing role of social networking platforms in public health discourse, they have tended to focus on information disclosure for diagnostic or predictive purposes -42, whilAs noted at the outset, the findings of this study may help public health officials and health care providers better leverage emerging technologies and engage with patients or the public in a more deliberate and targeted manner. By understanding the types of information that individuals seek or share on the web during periods of active infection, as well as how those behaviors correlate with key outcomes such as connectedness and anxiety, health professionals can more proactively engage with the public in digital spaces to ensure the availability of timely, effective, and reliable information. On the basis of the findings outlined above, we encourage public health officials and health care providers alike to proactively engage in the cultivation and maintenance of digital spaces that facilitate peer-to-peer information exchange amidst future outbreaks of COVID-19 and other acute public health crises. While these digital communities cannot (and should not) replace personalized interactions with health professionals, they offer the potential to provide patients with mental health and social support benefits that fall outside the scope of traditional health care services. This may be of particular value in instances such as the COVID-19 pandemic, which exacerbate social exclusion and health anxiety ,35. FurtWhile this study helps to demonstrate some of the risks and rewards of peer-to-peer information sharing and seeking among COVID-19–positive SNS users, there are some important limitations to keep in mind, as well as several opportunities for further examination of these trends. First, as part of a larger survey project examining attitudes around COVID-19 at the 3-year anniversary of the pandemic, constraints on questionnaire length prohibited us from collecting potentially relevant measures of household size, perceived social exclusion, and social capital. Each of these could potentially impact SNS users’ COVID-19 experiences and thus their decision to engage in peer-to-peer information sharing and seeking. However, it should be emphasized that during the COVID-19 pandemic, social isolation has increased even among those embedded in otherwise robust social networks. Additionally, the web-based nature of the data collection may result in some vulnerable population groups being underrepresented, including those with less than a high school diploma, residents in extremely remote rural settings, and non-English speakers.From a methodological perspective, the research design relies on patient recall, wherein respondents are asked to recall their web-based behaviors and experiences during periods of acute infection over the 3-year life span of the pandemic. In some cases, a significant amount of time may have elapsed since the respondent’s first COVID-19 diagnosis. While this may affect data quality in some cases, we believe that focusing on the respondents’ first COVID-19 experience optimizes data quality, as subsequent infections are likely to have resulted in significantly less ambiguity on the patient’s part . Additionally, we believe that the personal significance of COVID-19 diagnosis for patients makes it likely that their experiences are accurately recalled. With that in mind, additional research might focus on narrower and more recent recall windows in order to determine whether similar response patterns hold, whether in the context of COVID-19 or other acute illnesses. Finally, it is worth pointing out that the cross-sectional nature of the data collected in this study limits our ability to test causal statistical models, and while this type of data has been commonly used to understand web-based health behavior, future studies might benefit from a more longitudinal approach to measuring these relationships.Moving forward, we see opportunities to further develop and advance this line of research, including more nuanced data collection efforts that qualitatively measure the experiences of those who shared and sought peer-to-peer information on the web while infected with COVID-19. Along with considering different recall windows and using more longitudinal data techniques, this may also include a deeper examination of the content of specific posts shared and measures of social capital or isolation. Additionally, we recommend that future research use textual analysis to examine the content of social media posts containing peer-to-peer COVID-19 information exchanges, as this may help to further our understanding of both the content and impact of these interactions.


The change in the number of antiglaucoma agents in the administered eyedrops was not significant compared to the baseline values. At the end of the follow-up period the change in BCVA values was not significant (p = 0.655). Our results confirm significant IOP lowering effect of this subthreshold method preserving visual performance safely even in eyes with previous vitrectomy surgery with a silicone oil implantation.The aim of this study was to analyze the long-term outcome of first session of micropulse transscleral cyclophotocoagulation (MP-CPC) for refractory glaucoma developed after vitreoretinal surgery combined with silicone oil implantation. The inclusion criteria of this consecutive case series were: patients with secondary glaucoma in the refractory stage who underwent MP-CPC between 2018 and 2021, vitreoretinal surgery combined with silicon oil implantation, and at least a 24-month follow-up period after MP-CPC. Success was defined as the baseline eye pressure reduced at least 20%, and it should be ranged between 10 to 20 mmHg without further MP-CPC at the end of the follow-up. For this retrospective study, 11 eyes of 11 patients were selected. The reduction in IOP was found to be significant ( Glaucoma is a disease that leads to the progressive apoptosis of retinal ganglion cells, causing irreversible damage to the retinal nerve fiber layer and the optic nerve head. Secondary glaucoma is a heterogenous group of different conditions, such as uveitis, neovascularization in proliferative diabetic retinopathy or central retinal vein occlusion (CRVO), and iatrogenic causes. Iatrogenic secondary open-angle glaucoma includes cases in which a substance  used in the surgical treatment of a pre-existing disease  leads to higher intraocular pressure. The term refractory glaucoma is usually used in cases where the intraocular pressure is uncontrollably high despite maximum eyedrop therapy or when surgical methods  fail to reduce the intraocular pressure.Silicon oil implanted in the vitreous cavity can cause an increase in intraocular pressure in several ways: pupillary block glaucoma in aphakic eyes, overfilling of silicon oil, silicon oil migrating into the anterior chamber, and secondary chronic open or closed angle glaucoma . The migIn recent years, we have seen patients who have undergone silicone oil implantation for a more complicated vitreoretinal problem and developed difficult-to-treat secondary glaucoma. Despite maximum conservative treatment, the patient may experience pain in the eye or still loses vision after a successful vitreoretinal procedure due to high intraocular pressure. However, while MP-CPC is a well-documented effective adjuvant treatment method for several types of glaucoma see , very liThe aim of this preliminary study was to analyze the long-term outcome of MP-CPC for refractory glaucoma developed after vitreoretinal surgery combined silicone oil implantation for complicated posterior segment disease.It is a retrospective analysis of a consecutive case series. Medical records of 11 patients were analyzed; the data were extracted from Medsol system. Institutional Review Board approval was obtained for all study protocols (SE RKEB 193/2022). The inclusion criteria of this consecutive case series were: (1) patients who underwent MP-CPC between 2018 and 2021; (2) vitreoretinal surgery combined with silicon oil (1300 cst) implantation for complicated posterior segment disease; (3) at least 24-month follow-up period after MP-CPC; (4) no eye surgery was performed over a year before MP-CPC. Initially, we collected records of 13 patients, two of them were excluded. One patient was unable to attend follow-up visits after 9 months due to the COVID pandemic while the other patient had missed visits after 12 months due to pregnancy.Before MP-CPC and in the follow-up period, all of the patients underwent routine ophthalmic examination: best corrected visual acuity (BCVA) was measured on Early Treatment Diabetic Retinopathy Study (ETDRS) chart after automatic refractometry, slit lamp examination, Goldmann applanation tonometry, funduscopy. Intra and postoperative complications were monitored. Indications for MP-CPC were: (1) for 9 eyes, intraocular pressure ≥21 mmHg despite using personally tolerable eyedrops and oral acetazolamide combination  with or without oral carboanhydrase inhibitor or prostaglandine analog eyedrop); (2) concentrically narrowed visual field when intraocular pressure <21 mmHg for an eye of former premature patient, and this eye was managed with a combination of four drugs in the eyedrops. The reason for the visual field examination of the affected eye prior to MP-CPC was a suspected and confirmed concentric visual field narrowing due to retinopathy of prematurity and made even worse by secondary glaucoma. (3) The final indication was high intraocular pressure and severe pain in a blind eye of another former premature patient.The treatment was performed with a Supra 810 nm diode laser  at 3 mm from the limbus with a G-probe device, skipping the 3 and 9 o’clock regions . After the micropulse laser treatment, all patients received steroid eyedrop therapy for 2 weeks in addition to the previously prescribed anti-glaucoma eyedrops. The patients were asked to come for control quarterly (every three months). All complications, whether intraoperative, early, or late postoperative, were recorded. Special attention was paid to whether the surgery did not result in visible laser burn or subconjunctival suffusion. Major postoperative complications were considered to be significant visual impairment associated with MP-CPC, hypotony, phthisis. Anterior segment inflammation and transient BCVA deterioration within the first 2 postoperative weeks due to inflammation were classified as mild complications. All participants were treated in accordance with the tenets of the Declaration of Helsinki. Written informed consent was obtained from all participants.p-value of < 0.05 was considered statistically significant. Datasets are deposited in Dryad database .Statistical analysis was performed using IBM SPSS Statistics 25 . Therapeutic answer was characterized by the eye pressure; number of medications at baseline; 3, 6, 9, 12, 15, 24, 36, and 48 months; and the number of MP-CPC sessions during the follow-up. The changes in the best corrected visual acuity were also analyzed. A significant visual deterioration was defined as 2 or more lines worsening in BCVA measured on ETDRS chart. Loss rate was calculated at each follow-up time point. Loss rate means the ratio of number of patients who attended a visit and number of all patients who could have been followed based on the starting date (2018–2021). Success was defined as the baseline eye pressure reduced at least 20%, and it should be ranged between 10 to 20 mmHg at the end of follow-up. If 2 measurements occurred in the given quarter, the last was included in the analysis. Success rate was calculated at each follow-up point . Success rate is defined as number of eyes met the criteria of success at that given follow-up time point/total number of patients who could have been seen at that time. This means that (1) all patient who did not present were considered failures and, (2) due to the retrospective nature of the study, fewer patients were seen at the 36th and 48th month visits. The categorized values of eye pressure in the first 24 months were also estimated by chi-squared test. Wilcoxon signed rank test was performed to compare baseline and endpoint data of each eye. Friedman test was used to determine whether the repeated measurements of eye pressure and agent’s combination in the first 8 quarters differ from the baseline. Usage of oral acetazolamide at the end of follow-up of each patient was estimated by Fisher’s exact test. A Eleven eyes of eleven patients   met the Comorbidities of secondary glaucoma. The vitrectomies were performed between 2008 and 2019; the indications for silicon oil implantation were the following: retinal detachment with proliferative vitreoretinopathy in 5 eyes. Out of them one patient manifested rheumatoid arthritis (RA) and consecutive uveitis in both eyes. Another patient has ocular hypertension in the fellow eye. Two former premature patients suffered from retinal detachment caused by circular remnant of retinopathy of prematurity (ROP): one of them was blind for the fellow eye, the other patient’s operated eye had perforating sclera injury previously. In another patient, 2 quadrants large retinal tear developed with retinal detachment 8 months after an uncomplicated phacoemulsification for congenital cataract. The next patient had a perforating cornea injury and underwent vitrectomy combined perforating keratoplasty using a temporary prosthesis. Two type 1 insulin dependent diabetic patients had severe proliferative diabetic retinopathy.Complications. Mild acute complications, such as hyperemia or mild pain, occurred in seven and one patients, respectively. No severe complications were observed either intraoperatively or postoperatively. In the acute postoperative period, mild iritis was detected that resolved within 10 days using a steroid eyedrop. None of the patients developed a phthisis or hypotony during follow-up. No eyes became blind.Visual acuity. Except for 2 eyes, the original visual acuity could be preserved. One line worsening in BCVA occurred in 2 eyes, one line improvement was detected in another 2 eyes, and BCVA did not change in 4 eyes. In the remaining one eye was blind at the time of MP-CPC. Significant BCVA loss occurred in 2 eyes. One of them underwent an unsuccessful pars plana vitrectomy for retinal detachment 10 years before MP-CPC. The five lines of the deterioration of BCVA is determined by not only proliferative vitreoretinopathy, but also uveitic episodes due to rheumatoid arthritis. Rheumatoid arthritis was diagnosed a year after MP-CPC. In the first 2 years of the 5-year follow-up period of MP-CPC, iridocyclitis with macular edema developed 3 times in both eyes. The patient was unable to attend control examinations due to the COVID-19 pandemic. Three lines worsening in BCVA also occurred in the fellow eye, and secondary glaucoma was detected and required a shunt implantation. The other patient’s eye underwent a perforating keratoplasty combined pars plana vitrectomy for retinal detachment after a perforating cornea injury. In this case, the 5 lines of impairment in BCVA is explained by the corneal haze of the donor tissue.Intraocular pressure. In the first 2 years, the intraocular tension could be measured regularly: in a 3-month period in the first 15 months, after said period, and in a 6–8 month period, respectively. p = 0.004). Three patients required second session of MP-CPC, 6, 8, and 14 months after the first treatment, respectively (re-treatment rate 27%). The success rate of MP-CPC is 73% at the end of the first 2 years . Two patients achieved a 20% reduction; however, they even had an IOP above 20 mmHg (both of them had 26 mmHg with 23.50% IOP reduction). The third patient’s eye pressure was under 20 mmHg, but it was only a 10% reduction (18 mmHg). Out of these 3 patients, one eye failed at the end of 48 months of follow-up. This ROP eye was blind and contained silicon oil for 10 years at the time of MP-CPC. The combination of agents in eyedrops could be reduced in one eye, and it was achieved only in the first 3 months. For oral acetazolamide, at baseline, 6 patients used oral acetazolamide while at the end of follow-up of each patient, only 1 patient applied it (p = 0.0635), and the odds ratio is 12.00 at CI 95 1.117 to 128.9. We have to mention that at the 24-month follow-up point, no patient required oral acetazolamide. One patient required oral acetazolamide medication permanently over a year after MP-CPCP.plied it . The resTraditionally, cyclodestructive procedures are applied for otherwise non-treatable glaucoma. Transscleral CPC has a significant IOP lowering effect at 1, 5, and even 10 years. However, 51.5% of the treatments failed by the end of 10 years, and most failures occurred within the first year (40%). A high complication rate is reported in connection with this type of cyclodestructive procedure, such as a visual loss of two lines or more in 60% of patients and hypotony in 4% of eyes . A subcyIn this retrospective preliminary study, we aimed the evaluation of IOP control using subcyclo treatment in eyes with refractory secondary open angle glaucoma caused by silicon oil implantation after vitrectomy surgery. The cases had in common that they all turned out to be complicated , and all patients underwent silicon oil implantation. Despite the fact that the silicon oil was removed, filtration surgery to reduce IOP  was not an option in these cases due to the residual emulsified silicon oil particles. Our basic aim with the MP-CPC treatment was to reduce the patients’ pain by reducing the intraocular pressure and to preserve residual visual acuity by avoiding potential complications .IOP lowering. Our results confirm a significant IOP lowering effect of this subthreshold method, preserving visual performance safely even in eyes with previous vitrectomy surgery with silicone oil implantation . We cannot comment on a possible increased cataractogenesis since all of the patients underwent lens surgery several years before MP-CPC. Based on the literature data, possible complications of MP-CPC were collected in antation . The reddata see , the chaThe literature data on secondary glaucoma developed after the vitreoretinal procedure.prospective studies, except for the study of Zbiba et al., 2022 [l., 2022 , the othl., 2022 , Aquino l., 2022 , Barac el., 2022 , and Jaml., 2022 ) were nol., 2022  investigretrospective studies, 2 studies were found that included vitrectomized eyes. Lim et al., 2021 [As for the results of the l., 2021  investigl., 2021  comparedIt is difficult to compare the results of our study with the aforementioned studies, as most of them did not include vitrectomized eyes as a separate subgroup, and where it was analyzed as a separated subgroup, it was mentioned together with several other types of secondary glaucoma. However, our success rate was lower compared to the results in Zbiba et al.’s study. It was stable through the follow-up period. The differences might arise from the long-term history of silicon oil usage and the complex pathogenesis of glaucoma, including among other autoimmune uveitis, prematurity, trauma, and severe diabetic proliferative retinopathy. The limitations of our study are the retrospective design and the small number of patients. However, all of the patients underwent vitrectomy combined with silicone oil implantation, and the presented case series may not be representative for secondary glaucoma-induced silicone oil since many other factors are also implicated in the development of secondary glaucoma. This report should be considered as a preliminary study that requires further data validated from a greater number of patients treated in different centers.In conclusion, the manuscript provides real-life data on an uncommon but difficult-to-treat type of secondary glaucoma that develops after vitreoretinal surgery, related to silicone oil implantation but with a pathogenesis that is more complex than only silicone oil-induced. We found MP-CPC to be a safe and effective adjuvant treatment modality even in difficult cases, such as vitrectomized eyes.